Tools
Ehrlichiosis
Introduction
Ehrlichiosis is an emerging tick-borne, zoonotic infection caused by bacteria from the family Anaplasmataceae in the order Rickettsiales.[1][2] This disease is caused by several species of obligate, intracellular gram-negative coccobacilli transmitted to humans by infected tick bites, including Ehrlichia chaffeensis, E ewingii, E muris–like agent, and Anaplasma phagocytophilum.[3][4] Although all these intracellular coccobacilli cause ehrlichiosis with similar clinical symptoms, their geographic distribution and severity may differ. E chaffeensis and A phagocytophilum can cause more severe disease. Patients typically complain of nonspecific symptoms such as headaches and flu-like symptoms. Laboratory findings may include thrombocytopenia, leukopenia, anemia, liver function test abnormalities, and even acute kidney failure, depending on the type of species they are infected with.[3] Ehrlichiosis is a potentially life-threatening and fatal disease in humans and should be recognized and treated promptly.
Clinically, ehrichiosis presents many common symptoms and signs with rickettsial infections and may share overlapping geographic distribution.[5] Clinicians should consider Ehrlichia infections when evaluating patients with flu-like illnesses in endemic areas. Due to the expanding geographic range of the ticks and the reservoirs of the species that cause ehrlichiosis, it is essential to be up-to-date regarding the changing epidemiology of Ehrlichia infections. Prompt administration of doxycycline significantly improves outcomes, and treatment should not be delayed pending diagnostic confirmation. Increased awareness, prompt diagnosis, and timely treatment are necessary for good patient outcomes.
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
E chaffeensis, E ewingii, E muris–like agent, and A phagocytophilum are the organisms that cause ehrlichiosis in humans.[6] E chaffeensis and A phagocytophilum are the most frequent causes of ehrlichiosis in North America and cause the most severe infections.[4][7] E ewingii, discovered in 1999, is a canine pathogen that can also cause human disease called human ewingii ehrlichiosis.[6] E muris–like agent was first identified as the cause of human infections in Wisconsin and Minnesota in 2009.[8]
E chaffeensis, E canis, and E muris are intracellular coccobacilli with a tropism for monocytes and macrophages in their hosts. E chaffeensis, which was initially identified in 1986, is the cause of human monocytic ehrlichiosis, the most common ehrlichiosis in North America and the most severe disease out of all the ehrlichioses.[9][10] The reservoir for E chaffeensis is the white-tailed deer (Odocoileus virginianus), and the disease is transmitted by the lone star tick (Amblyomma americanum) and, more rarely, by other ticks, such as the American dog tick (Dermacentor variabilis). E ewingii is also transmitted by the lone star tick (A americanum).[6] E canis mostly infects dogs but is also known to affect humans and is transmitted by the brown dog tick (Rhipicephalus sanguineus).[9][11] E muris–like agent was first identified as the cause of human infections in Wisconsin and Minnesota in 2009 and is transmitted in the United States by Ixodes cookei and I scapularis ticks, by Haemaphysalis flava ticks in Japan, by I persulcatus ticks in Eastern Europe, and by I ricinus ticks in Western Europe.[6][12]
Another species within this genus, E ruminantium, is primarily transmitted by ticks of the Amblyomma genus. E ruminantium causes heartwater, a fatal disease in ruminant animals in tropical areas, and can occasionally infect humans.[13]
Human granulocytic anaplasmosis was originally named Rickettsia phagocytophila and was later renamed to Cytoecetes phagocytophila, E phagocytophila, E equi, and then human granulocytic ehrlichiosis (HGE).[14] This finding has now been recognized that E phagocytophila and E equi are the same organism, renamed A phagocytophilum.[15] This organism primarily infects granulocytes, as observed in blood smear examinations.[3][16][17] Human granulocytic anaplasmosis is found in the United States, Europe, and Asia[17]
A phagocytophilum causes human granulocytic anaplasmosis and is transmitted by the tick I scapularis on the East Coast, which also transmits E muris–like agent, Borrelia burgdorferi, and Babesia microt, and I pacificus ticks on the West Coast of the United States.[2][3][4] Most cases have been reported from the upper Midwest and the Northeast of the United States. Human granulocytic anaplasmosis has also been reported in Northern Europe and Southeast Asia, with other vectors such as I ricinus.[18] Human granulocytic anaplasmosis was originally identified in 1990 in the Upper Midwest states in the United States. Life-threatening complications develop in up to 3% of patients, and nearly 1% succumb to the infection.[19]
Epidemiology
Ehrlichiosis and anaplasmosis are emerging infections in the United States and worldwide. In the United States, these infections are the most frequently recorded tick-borne diseases after Lyme disease, with estimated case fatality rates of 2.7% and 0.3%, respectively [20][21]. The increase in these tick-borne diseases is a public health concern because the tick population is increasing mainly due to climate change. The geographic distribution of ticks is expanding, and more cases are being reported.[20][22] Efforts to perform surveillance are being used to understand the ecology and distribution of the ticks, their reservoirs, and the endemic areas for infections transmitted through ticks.[20]
The first Ehrlichia species, E chaffeensis, was identified in the United States relatively recently in 1986 and in Europe in 1991 from Portugal.[23] Since then, newer species, even those believed to cause disease only in animals, such as E canis and E ewingii, have been found to cause disease in humans.[24] E chaffeensis and E ewingii are transmitted by the lone star tick, Amblyomma americanum, and their most crucial reservoir is the white-tailed deer, the host for the whole life cycle of the lone star tick (A americanum).[22] Infections are reported most commonly during the spring and summer months, coincident with the adult and nymphal stages of the tick life cycle, in which ticks are most likely to bite humans due to outdoor activities[5]. E chaffeensis occurs predominantly in areas where the lone star tick (A americanum) is prevalent, such as the South Central United States. According to data from the Centers for Disease Control and Prevention (CDC), over 30% of reported Ehrlichia infections in the United States were from Oklahoma, Missouri, and Arkansas.[22] Recently, E chaffeensis has been slowly spreading and is increasingly found in the Northeast and North-Central United States.
The changing epidemiology of Ehrlichia and the geographical distribution of the reservoir, the white-tailed deer, and the lone star tick depend on many factors.[20] Abiotic factors, such as temperature and humidity, and biotic factors, such as vegetation density and shade, along with climate change, result in warmer temperatures in higher latitudes and can increase the geographic expansion of vectors and reservoirs.[20][25] Changes in the white-tailed deer populations, for any reason, affect the epidemiology of human monocytic ehrlichiosis. Since the first reports of human monocytic ehrlichiosis, the number of reported cases increased from 338 in 2004 to 1377 in 2006 and 7309 newly reported cases between 2013 and 2017. Most of these cases were from New York, Virginia, Missouri, and Arkansas.[20][26] The reported incidence of E chaffeensis from 2000 to 2007 increased from 0.80 to 3.0 cases per million persons per year, and the case fatality rate and hospitalization rates were 1.9% and 49%, respectively.[15] From 2008 to 2012, 4613 cases of E chaffeensis and 55 cases of E ewingii were reported through the CDC in the United States.[22] The incidence rate was 3.2 cases per million person-years, the hospitalization rate was 57%, and the case fatality rate was 1%. The highest case fatality rate was 4%, reported in children younger than 5. Until 2012, the rate of ehrlichiosis had increased 4-fold since 2000.[22]
Symptoms may range from mild to severe and can even be fatal if not treated, especially if infected with E chaffeensis and A phagocytophilum. Patients who are older or immunocompromised may have worse outcomes if not treated promptly. Ehrlichiosis and anaplasmosis can also be transmitted through blood transfusions, which have been increasingly reported, especially in patients with hematological or solid tumor malignancies and transplantation.[27] Cases in adults and children can be mild and subclinical, or clinicians may not consider the disease in the differential diagnosis. Thus, the disease may be underdiagnosed and under-reported.[28][29]
A phagocytophilum is primarily reported in the Northeast United States and is transmitted by the I scapularis tick in the upper Midwest, and the I pacificus tick on the West Coast of the United States. The reservoirs are the white-tailed deer and the white-footed mouse. Recorded cases of anaplasmosis rose from 537 in 2004 to 4151 cases in 2016; in a recent report, 4151 cases were reported annually.[30] Human granulocytic anaplasmosis can be severe, with 36% of patients requiring hospitalization and 3% with life-threatening complications.[19][31] Other reports have stated that up to 17% of hospitalized patients required admission to the intensive care unit.[19]
Pathophysiology
Infection with Ehrlichia species begins with the intracellular uptake of the infectious extracellular form of the organism, the elementary body or dense core. The elementary body or dense core is then taken up by endocytosis, where the organism replicates and matures to form a reticulate body or reticulate core and then morula before redifferentiating into an elementary body/dense core that leaves the infected host cell to spread infection.[32] During this process, Ehrlichia uses several immune evasion mechanisms, including suppression of host cell apoptosis, modulation of chemokine and cytokine responses, and downregulation of host pattern recognition receptors that might enable clearance of the infection.
Ehrlichia preferentially infects peripheral blood leukocytes, with E chaffeensis associated with human monocytic cells, including monocytes and macrophages, and neutrophil infections reported in E ewingii. Multiorgan involvement can occur, with organisms detected in the spleen, lymph nodes, bone marrow, and peripheral blood. The clinical manifestations of Ehrlichia infections appear to be due to the host's inflammatory response to the infection rather than direct damage from the bacteria.[33][34][33]
History and Physical
Obtaining a detailed history and performing a thorough clinical examination are crucial for all patients seeking medical care. Human monocytic ehrlichiosis and human granulocytic anaplasmosis have an incubation period of 1 to 2 weeks following a tick bite, with a median of 9 days.[35]. These diseases typically present as acute illnesses ranging from asymptomatic to severe.
A detailed exposure history should be obtained, including details about outdoor activities, travel to endemic areas, encounters with ticks, and use of insect repellant. A family history of recent illness should also be obtained to determine whether anyone in the household has similar symptoms. As patients may not be aware of a tick bite, clinicians should ask targeted questions regarding any potential bites or rashes.
Diagnosing human monocytic ehrlichiosis and human granulocytic anaplasmosis should be strongly considered when patients have symptoms compatible with the disease and have the appropriate epidemiology, such as exposure to wooded areas in spring or summer. Patients with Ehrlichia infections, regardless of organism, typically present with nonspecific, flu-like symptoms such as fever, malaise, headache, body aches, and chills.[36] Other findings may include gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and rash. Cough and respiratory symptoms are more common in adults compared to children. The central nervous system may also be involved, leading to symptoms such as a stiff neck and headache, along with cerebrospinal fluid analysis indicating meningitis and meningoencephalitis.[36][37] Less than 30% of adults and more than 60% of children develop a rash, although Anaplasmosis rarely causes a rash. The rash typically presents 5 to 7 days into the illness as a maculopapular, petechiae, or diffuse erythema, commonly on the extremities, but may occasionally involve the palms and soles.[36] Co-infections with other tick-borne diseases, such as B burgdorferi, the causative agent of Lyme disease, which leads to erythema migrans, should be considered when diagnosing rashes.
In some patients who have more severe early symptoms or in those who have been left untreated, symptoms may progress to acute respiratory distress syndrome or sepsis or shock-like presentation with cardiovascular instability and coagulopathy.[36] However, overall mortality is much lower in ehrlichiosis than in rickettsial disease but higher than in Lyme disease. The CDC reports a 1% to 3% mortality rate since 2000 in patients who present for medical care of ehrlichiosis [36]. Anaplasmosis can be severe, with 36% of patients requiring hospitalization and 3% with life-threatening complications.[19][31] Other reports have stated that up to 17% of hospitalized patients required admission to the intensive care unit.[19] Many patients may be infected with ehrlichiosis but may not seek medical care, potentially leading to an overestimation of the mortality rate. Immunocompromised individuals, older adults, or those who have received pretreatment with sulfonamide antibiotics are predisposed to more severe illness.[38][39][40][41]
Complications of human monocytic ehrlichiosis and human granulocytic anaplasmosis may include respiratory and renal failure and neurological disease, such as coma and seizures.[37] There have also been reports of hemophagocytic lymphohistiocytosis.[42] Early recognition and treatment of ehrlichiosis and other tick-borne diseases are crucial, as prompt antibiotic therapy significantly improves outcomes.[36]
Evaluation
Patients with human monocytic ehrlichiosis or human granulocytic anaplasmosis have a wide range of symptoms and laboratory findings, but there are some characteristic findings. These include leukopenia, thrombocytopenia, and mild to moderately elevated transaminases. Hyponatremia and elevated creatinine may also be present.[3][36] In some cases, morulae may be present in the peripheral blood or other body fluids of a patient with ehrlichiosis.[36] Cerebrospinal leukocytosis and mildly elevated protein levels may also occur. Anemia occurs in 50% of patients, typically later in the disease course.[36]
Laboratory confirmation is critical for a definite diagnosis, which can be performed through serology or polymerase chain reaction testing to detect DNA. Polymerase chain reaction is highly sensitive during acute illness and within the first week of infection.[3] Serological confirmation of immunoglobulin M (IgM) and IgG antibodies specific to E chaffeensis can be achieved through indirect immunofluorescence assay using paired sera.[3] A positive serology is defined as either a single IgG antibody titer of 256 or higher or a 4-fold increase in IgG antibody titer between paired serum samples and at least one of the IgG titers to be at least 1:64 to 1:80.[36] A drawback of using serological diagnosis is that it is limited by the time it takes for seroconversion and can be user-dependent.[36]
Due to the rapidly progressing nature and potential severity of these infections, empiric therapy should not be delayed, but confirmatory testing should still be performed. The initial diagnosis can be based on the clinical picture, endemic tick-borne infections, and laboratory values.
Treatment / Management
Doxycycline is the preferred drug for treating ehrlichiosis.[36] The recommended dosage of doxycycline is 100 mg twice daily (orally or intravenously) for adults and 2.2 mg/kg body weight twice daily (orally or intravenously) for children weighing less than 45 kg.[36] Previous guidelines that restricted doxycycline use to children older than 8 years have been updated, as clinical studies have shown no evidence of dental staining in younger children. As a result, doxycycline is now recommended for all children, regardless of age.[43][44] There is no recommendation for post-tick bite prophylaxis against ehrlichiosis in endemic areas.[45][46]
Patients with ehrlichiosis typically defervesce in 48 to 72 hours after starting doxycycline. The usual treatment duration is 7 to 10 days, depending on the severity of the illness, and should be continued for an additional 3 days after defervescence.[35]
Differential Diagnosis
The differential diagnosis for ehrlichiosis includes any nonspecific flu-like syndrome. The diagnosis can be more directed if the syndrome includes fever, malaise, cytopenias, elevated liver function tests, and a history of tick exposure.
- Tick-borne diseases such as R rickettsii, Babesiosia microti, and B burgdorferi
- Neisseria meningitidis
- Epstein-Barr virus infection or infectious mononucleosis
- Cytomegalovirus infection
- Dengue fever
- Malaria
- Influenza
- Bacterial sepsis
- Endocarditis
- Systemic lupus erythematosus
- Hemophagocytic lymphohistiocytosis
- Hematological malignancies, such as lymphoma and leukemia
- Hepatitis
- Kawasaki disease
- Leptospirosis
- Q fever
- Toxic shock syndrome
- Typhoid fever
Prognosis
Ehrlichiosis generally responds well when diagnosed and treated promptly, with symptomatic improvement typically observed within 24 to 48 hours. The recommended treatment duration is 7 to 10 days. Early initiation of doxycycline is associated with improved outcomes.[47] However, if treatment is delayed or if the patient has an underlying chronic illness, malignancy, immunosuppression, or is an older adult, the disease can be severe and even fatal.[47] Complications such as adult respiratory distress syndrome, shock, disseminated intravascular coagulation–like syndrome, central nervous system involvement, and renal failure may develop. Therefore, empiric therapy should be initiated as soon as ehrlichiosis is suspected, even before laboratory confirmation.[48]
Complications
In rare instances, particularly in patients with a weak immune system, such as those with HIV or cancer, ehrlichiosis can lead to serious complications, including:
- Neurological issues, such as confusion, seizures, or coma
- Hemorrhage
- Heart failure
- Respiratory failure
- Kidney failure
- Septic shock
These complications may require additional treatment, including respiratory support, intravenous fluids, or kidney dialysis. Complications are more prevalent in older patients, immunosuppressed individuals, or those with pre-existing health conditions.[35]
Deterrence and Patient Education
Patients should be educated on best practices for tick prevention. There is no human-to-human transmission of ehrlichiosis. The most important deterrent is the prevention of tick bites, especially in endemic areas. Wearing protective clothing, such as long pants tucked into socks, is essential to minimize skin exposure.[49]
In addition to clothing, repellants are mandatory when performing outdoor activities. Effective repellants include N,N-diethyl-meta-toluamide, picaridin, and IR3535. Daily body checks for ticks, especially in warm, moist areas, such as the axillae, groin, and neck, are important for early detection and removal of ticks.[49][50][49]
Pearls and Other Issues
There is no vaccine available for any of the Ehrlichia species. Avoiding tick bites remains the mainstay of prevention, with insect repellents, avoiding high-risk areas, covering all exposed skin, and checking carefully for ticks after outdoor activities in endemic areas. As ehrlichiosis is not transmitted directly person-to-person, no isolation is needed.
Enhancing Healthcare Team Outcomes
Most patients with Ehrlichia infections typically seek medical attention either at the emergency department or through their primary care providers. Due to the nonspecific nature of the symptoms associated with Ehrlichia infection, it is crucial for healthcare professionals to consult with an infectious disease specialist early in the diagnosis and management process. The infection can manifest in various ways, potentially affecting the skin, central nervous system, gastrointestinal tract, and muscular systems, or it may even present as shock. Since 2000, the CDC has reported mortality rates ranging from 1% to 3% among patients who seek medical care for ehrlichiosis. However, it is essential to recognize that many individuals may be infected without presenting for medical evaluation, which could result in an overestimation of the mortality rate associated with this disease.
When infected with Ehrlichia, certain populations are at higher risk for more severe illness. Immunocompromised individuals, older patients, or those who have previously received treatment with sulfonamide antibiotics may experience exacerbated symptoms and complications. These factors increase the likelihood of serious outcomes, underscoring the importance of early recognition and treatment of ehrlichiosis. Prompt intervention enhances the chances of a favorable outcome and mitigates the risks of severe complications, highlighting the critical role of timely medical assessment and expert consultation in managing this potentially life-threatening infection.
References
Rikihisa Y. The "Biological Weapons" of Ehrlichia chaffeensis: Novel Molecules and Mechanisms to Subjugate Host Cells. Frontiers in cellular and infection microbiology. 2021:11():830180. doi: 10.3389/fcimb.2021.830180. Epub 2022 Jan 14 [PubMed PMID: 35155275]
Dumler JS, Barbet AF, Bekker CP, Dasch GA, Palmer GH, Ray SC, Rikihisa Y, Rurangirwa FR. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila. International journal of systematic and evolutionary microbiology. 2001 Nov:51(Pt 6):2145-2165. doi: 10.1099/00207713-51-6-2145. Epub [PubMed PMID: 11760958]
Level 1 (high-level) evidenceIsmail N, Bloch KC, McBride JW. Human ehrlichiosis and anaplasmosis. Clinics in laboratory medicine. 2010 Mar:30(1):261-92. doi: 10.1016/j.cll.2009.10.004. Epub [PubMed PMID: 20513551]
Schudel S, Gygax L, Kositz C, Kuenzli E, Neumayr A. Human granulocytotropic anaplasmosis-A systematic review and analysis of the literature. PLoS neglected tropical diseases. 2024 Aug:18(8):e0012313. doi: 10.1371/journal.pntd.0012313. Epub 2024 Aug 5 [PubMed PMID: 39102427]
Level 1 (high-level) evidenceRochlin I, Toledo A. Emerging tick-borne pathogens of public health importance: a mini-review. Journal of medical microbiology. 2020 Jun:69(6):781-791. doi: 10.1099/jmm.0.001206. Epub 2020 Jun 1 [PubMed PMID: 32478654]
Buller RS, Arens M, Hmiel SP, Paddock CD, Sumner JW, Rikhisa Y, Unver A, Gaudreault-Keener M, Manian FA, Liddell AM, Schmulewitz N, Storch GA. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. The New England journal of medicine. 1999 Jul 15:341(3):148-55 [PubMed PMID: 10403852]
Dumic I, Jevtic D, Veselinovic M, Nordstrom CW, Jovanovic M, Mogulla V, Veselinovic EM, Hudson A, Simeunovic G, Petcu E, Ramanan P. Human Granulocytic Anaplasmosis-A Systematic Review of Published Cases. Microorganisms. 2022 Jul 15:10(7):. doi: 10.3390/microorganisms10071433. Epub 2022 Jul 15 [PubMed PMID: 35889152]
Level 1 (high-level) evidencePritt BS, Sloan LM, Johnson DK, Munderloh UG, Paskewitz SM, McElroy KM, McFadden JD, Binnicker MJ, Neitzel DF, Liu G, Nicholson WL, Nelson CM, Franson JJ, Martin SA, Cunningham SA, Steward CR, Bogumill K, Bjorgaard ME, Davis JP, McQuiston JH, Warshauer DM, Wilhelm MP, Patel R, Trivedi VA, Eremeeva ME. Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009. The New England journal of medicine. 2011 Aug 4:365(5):422-9. doi: 10.1056/NEJMoa1010493. Epub [PubMed PMID: 21812671]
Gygax L, Schudel S, Kositz C, Kuenzli E, Neumayr A. Human monocytotropic ehrlichiosis-A systematic review and analysis of the literature. PLoS neglected tropical diseases. 2024 Aug:18(8):e0012377. doi: 10.1371/journal.pntd.0012377. Epub 2024 Aug 2 [PubMed PMID: 39093857]
Level 1 (high-level) evidencePaddock CD, Childs JE. Ehrlichia chaffeensis: a prototypical emerging pathogen. Clinical microbiology reviews. 2003 Jan:16(1):37-64 [PubMed PMID: 12525424]
Perez M, Bodor M, Zhang C, Xiong Q, Rikihisa Y. Human infection with Ehrlichia canis accompanied by clinical signs in Venezuela. Annals of the New York Academy of Sciences. 2006 Oct:1078():110-7 [PubMed PMID: 17114689]
Xu G, Pearson P, Rich SM. Ehrlichia muris in Ixodes cookei Ticks, Northeastern United States, 2016-2017. Emerging infectious diseases. 2018 Jun:24(6):1143-1144. doi: 10.3201/eid2406.171755. Epub [PubMed PMID: 29774863]
Conrad ME. Ehrlichia canis: a tick-borne rickettsial-like infection in humans living in the southeastern United States. The American journal of the medical sciences. 1989 Jan:297(1):35-7 [PubMed PMID: 2643878]
Woldehiwet Z. The natural history of Anaplasma phagocytophilum. Veterinary parasitology. 2010 Feb 10:167(2-4):108-22. doi: 10.1016/j.vetpar.2009.09.013. Epub 2009 Sep 20 [PubMed PMID: 19811878]
Dahlgren FS, Mandel EJ, Krebs JW, Massung RF, McQuiston JH. Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000-2007. The American journal of tropical medicine and hygiene. 2011 Jul:85(1):124-31. doi: 10.4269/ajtmh.2011.10-0613. Epub [PubMed PMID: 21734137]
Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA. 1994 Jul 20:272(3):212-8 [PubMed PMID: 8022040]
Severo MS, Stephens KD, Kotsyfakis M, Pedra JH. Anaplasma phagocytophilum: deceptively simple or simply deceptive? Future microbiology. 2012 Jun:7(6):719-31. doi: 10.2217/fmb.12.45. Epub [PubMed PMID: 22702526]
Matei IA, Estrada-Peña A, Cutler SJ, Vayssier-Taussat M, Varela-Castro L, Potkonjak A, Zeller H, Mihalca AD. A review on the eco-epidemiology and clinical management of human granulocytic anaplasmosis and its agent in Europe. Parasites & vectors. 2019 Dec 21:12(1):599. doi: 10.1186/s13071-019-3852-6. Epub 2019 Dec 21 [PubMed PMID: 31864403]
Bakken JS, Dumler JS. Human granulocytic anaplasmosis. Infectious disease clinics of North America. 2015 Jun:29(2):341-55. doi: 10.1016/j.idc.2015.02.007. Epub [PubMed PMID: 25999228]
Alkishe A, Raghavan RK, Peterson AT. Likely Geographic Distributional Shifts among Medically Important Tick Species and Tick-Associated Diseases under Climate Change in North America: A Review. Insects. 2021 Mar 5:12(3):. doi: 10.3390/insects12030225. Epub 2021 Mar 5 [PubMed PMID: 33807736]
Dixon DM, Branda JA, Clark SH, Dumler JS, Horowitz HW, Perdue SS, Pritt BS, Sexton DJ, Storch GA, Walker DH. Ehrlichiosis and anaplasmosis subcommittee report to the Tick-borne Disease Working Group. Ticks and tick-borne diseases. 2021 Nov:12(6):101823. doi: 10.1016/j.ttbdis.2021.101823. Epub 2021 Sep 4 [PubMed PMID: 34517150]
Nichols Heitman K, Dahlgren FS, Drexler NA, Massung RF, Behravesh CB. 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. The American journal of tropical medicine and hygiene. 2016 Jan:94(1):52-60. doi: 10.4269/ajtmh.15-0540. Epub 2015 Nov 30 [PubMed PMID: 26621561]
Morais JD, Dawson JE, Greene C, Filipe AR, Galhardas LC, Bacellar F. First European case of ehrlichiosis. Lancet (London, England). 1991 Sep 7:338(8767):633-4 [PubMed PMID: 1679172]
Level 3 (low-level) evidenceMaeda K, Markowitz N, Hawley RC, Ristic M, Cox D, McDade JE. Human infection with Ehrlichia canis, a leukocytic rickettsia. The New England journal of medicine. 1987 Apr 2:316(14):853-6 [PubMed PMID: 3029590]
Bouchard C, Dibernardo A, Koffi J, Wood H, Leighton PA, Lindsay LR. N Increased risk of tick-borne diseases with climate and environmental changes. Canada communicable disease report = Releve des maladies transmissibles au Canada. 2019 Apr 4:45(4):83-89. doi: 10.14745/ccdr.v45i04a02. Epub 2019 Apr 4 [PubMed PMID: 31285697]
Maxwell SP, Brooks C, Kim P, Kim D, McNeely CL, Thomas K. Understanding Habitats and Environmental Conditions of White-Tailed Deer Population Density and Public Health Data to Aid in Assessing Human Tick-Borne Disease Risk. Microorganisms. 2023 Mar 28:11(4):. doi: 10.3390/microorganisms11040865. Epub 2023 Mar 28 [PubMed PMID: 37110288]
Level 3 (low-level) evidenceMasterson EM, Gupta S, Jakharia N, Peacock JE Jr. 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. Transplant infectious disease : an official journal of the Transplantation Society. 2020 Aug:22(4):e13299. doi: 10.1111/tid.13299. Epub 2020 May 5 [PubMed PMID: 32306509]
Level 3 (low-level) evidencePaulino PG, Pires MS, da Silva CB, Peckle M, da Costa RL, Vitari GV, Vilela JAR, de Abreu APM, Massard CL, Santos HA. Epidemiology of Ehrlichia canis in healthy dogs from the Southeastern region of the state of Rio de Janeiro, Brazil. Preventive veterinary medicine. 2018 Nov 1:159():135-142. doi: 10.1016/j.prevetmed.2018.09.012. Epub 2018 Sep 14 [PubMed PMID: 30314776]
Springer YP, Johnson PTJ. Large-scale health disparities associated with Lyme disease and human monocytic ehrlichiosis in the United States, 2007-2013. PloS one. 2018:13(9):e0204609. doi: 10.1371/journal.pone.0204609. Epub 2018 Sep 27 [PubMed PMID: 30261027]
Madison-Antenucci S, Kramer LD, Gebhardt LL, Kauffman E. Emerging Tick-Borne Diseases. Clinical microbiology reviews. 2020 Mar 18:33(2):. doi: 10.1128/CMR.00083-18. Epub 2020 Jan 2 [PubMed PMID: 31896541]
Russell A, Prusinski M, Sommer J, O'Connor C, White J, Falco R, Kokas J, Vinci V, Gall W, Tober K, Haight J, Oliver J, Meehan L, Sporn LA, Brisson D, Backenson PB. Epidemiology and Spatial Emergence of Anaplasmosis, New York, USA, 2010‒2018. Emerging infectious diseases. 2021 Aug:27(8):2154-2162. doi: 10.3201/eid2708.210133. Epub [PubMed PMID: 34287128]
Moumène A, Meyer DF. Ehrlichia's molecular tricks to manipulate their host cells. Microbes and infection. 2016 Mar:18(3):172-9. doi: 10.1016/j.micinf.2015.11.001. Epub 2015 Nov 23 [PubMed PMID: 26617397]
Ismail N, Sharma A, Soong L, Walker DH. Review: Protective Immunity and Immunopathology of Ehrlichiosis. Zoonoses (Burlington, Mass.). 2022 Jan 6:2(1):. doi: 10.15212/zoonoses-2022-0009. Epub 2022 Jul 5 [PubMed PMID: 35876763]
McBride JW, Walker DH. Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies. Expert reviews in molecular medicine. 2011 Jan 31:13():e3. doi: 10.1017/S1462399410001730. Epub 2011 Jan 31 [PubMed PMID: 21276277]
Pace EJ, O'Reilly M. Tickborne Diseases: Diagnosis and Management. American family physician. 2020 May 1:101(9):530-540 [PubMed PMID: 32352736]
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. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2016 May 13:65(2):1-44. doi: 10.15585/mmwr.rr6502a1. Epub 2016 May 13 [PubMed PMID: 27172113]
Iyamu O, Ciccone EJ, Schulz A, Sung J, Abernathy H, Alejo A, Tyrlik K, Arahirwa V, Mansour O, Giandomenico D, Diaz MM, Boyce RM. Neurological manifestations of ehrlichiosis among a cohort of patients: prevalence and clinical symptoms. BMC infectious diseases. 2024 Jul 17:24(1):701. doi: 10.1186/s12879-024-09607-3. Epub 2024 Jul 17 [PubMed PMID: 39020279]
Im JH, Baek J, Durey A, Kwon HY, Chung MH, Lee JS. Current Status of Tick-Borne Diseases in South Korea. Vector borne and zoonotic diseases (Larchmont, N.Y.). 2019 Apr:19(4):225-233. doi: 10.1089/vbz.2018.2298. Epub 2018 Oct 17 [PubMed PMID: 30328790]
Khamesipour F, Dida GO, Anyona DN, Razavi SM, Rakhshandehroo E. Tick-borne zoonoses in the Order Rickettsiales and Legionellales in Iran: A systematic review. PLoS neglected tropical diseases. 2018 Sep:12(9):e0006722. doi: 10.1371/journal.pntd.0006722. Epub 2018 Sep 11 [PubMed PMID: 30204754]
Level 1 (high-level) evidencePujalte GGA, Marberry ST, Libertin CR. Tick-Borne Illnesses in the United States. Primary care. 2018 Sep:45(3):379-391. doi: 10.1016/j.pop.2018.05.011. Epub 2018 Jul 9 [PubMed PMID: 30115329]
Eisen RJ, Eisen L. The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern. Trends in parasitology. 2018 Apr:34(4):295-309. doi: 10.1016/j.pt.2017.12.006. Epub 2018 Jan 11 [PubMed PMID: 29336985]
Patel TP, Beck P, Chairman D, Regunath H. Ehrlichiosis Presenting as Hemophagocytic Lymphohistiocytosis in an Immunocompetent Adult. IDCases. 2020:20():e00813. doi: 10.1016/j.idcr.2020.e00813. Epub 2020 May 12 [PubMed PMID: 32455115]
Level 3 (low-level) evidenceStultz JS, Eiland LS. Doxycycline and Tooth Discoloration in Children: Changing of Recommendations Based on Evidence of Safety. The Annals of pharmacotherapy. 2019 Nov:53(11):1162-1166. doi: 10.1177/1060028019863796. Epub 2019 Jul 7 [PubMed PMID: 31280586]
Todd SR, Dahlgren FS, Traeger MS, Beltrán-Aguilar ED, Marianos DW, Hamilton C, McQuiston JH, Regan JJ. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. The Journal of pediatrics. 2015 May:166(5):1246-51. doi: 10.1016/j.jpeds.2015.02.015. Epub 2015 Mar 17 [PubMed PMID: 25794784]
Ismail N, McBride JW. Tick-Borne Emerging Infections: Ehrlichiosis and Anaplasmosis. Clinics in laboratory medicine. 2017 Jun:37(2):317-340. doi: 10.1016/j.cll.2017.01.006. Epub 2017 Mar 25 [PubMed PMID: 28457353]
Saito TB, Walker DH. Ehrlichioses: An Important One Health Opportunity. Veterinary sciences. 2016 Aug 31:3(3):. doi: 10.3390/vetsci3030020. Epub 2016 Aug 31 [PubMed PMID: 29056728]
Kuriakose K, Pettit AC, Schmitz J, Moncayo A, Bloch KC. Assessment of Risk Factors and Outcomes of Severe Ehrlichiosis Infection. JAMA network open. 2020 Nov 2:3(11):e2025577. doi: 10.1001/jamanetworkopen.2020.25577. Epub 2020 Nov 2 [PubMed PMID: 33201233]
Mylonakis ME, Harrus S, Breitschwerdt EB. An update on the treatment of canine monocytic ehrlichiosis (Ehrlichia canis). Veterinary journal (London, England : 1997). 2019 Apr:246():45-53. doi: 10.1016/j.tvjl.2019.01.015. Epub 2019 Feb 4 [PubMed PMID: 30902188]
McCarthy CA, Helis JA, Daikh BE. Lyme Disease in Children. Infectious disease clinics of North America. 2022 Sep:36(3):593-603. doi: 10.1016/j.idc.2022.03.002. Epub [PubMed PMID: 36116837]
Eisen L. Personal protection measures to prevent tick bites in the United States: Knowledge gaps, challenges, and opportunities. Ticks and tick-borne diseases. 2022 Jul:13(4):101944. doi: 10.1016/j.ttbdis.2022.101944. Epub 2022 Mar 26 [PubMed PMID: 35364518]