Ehrlichiosis


Article Author:
Jessica Snowden


Article Editor:
Kari Simonsen


Editors In Chief:
Venkat Minnaganti
John Brusch
Janak Koirala


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Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
4/16/2019 11:45:31 PM

Introduction

The genus Ehrlichia consists of several species of obligate intracellular gram-negative bacteria that infect humans and a variety of other mammals via tick bite. Clinically, Ehrlichia infections share many symptoms and geographic distribution with rickettsial infections and thus, one must also consider Ehrlichia infections when evaluating patients with flu-like illnesses in endemic areas.[1][2][3]

Etiology

The genus Ehrlichia includes Ehrlichia chaffeesis, which causes human monocytic ehrlichiosis (HME) and Ehrlichia ewingii, which causes Ehrlichia ewingii ehrlichiosis. Other species within this genus include Ehrlichia canis and Ehrlichia ruminantium, which are predominantly veterinary pathogens but may also occasionally infect humans, and the recently described EMLA (Ehrlichia muris-like agent), which also has been associated with human disease. Ehrlichia are intracellular, gram-negative organisms transmitted via tick bite and are capable of replicating in both the tick and the infected host. In addition to humans, other hosts include dogs, cattle, sheep, goats, rodents, and deer.

Epidemiology

The frequency of Ehrlichia diagnoses is increasing, which is thought to be due to an increase in recognition and diagnostic availability as well the expansion of the regions in which the most common tick vector, the Lone Star tick (Amblyomma americanum) resides. Most Ehrlichia infections in the United States are due to Ehrlichia chaffeesis, with Ehrlichia ewingii reported less frequently. Ehrlichia infections occur predominantly in areas in which the Lone Star tick (Amblyomma americanum) is prevalent, such as the South Central United States. According to Centers for Disease Control and Prevention data, over 30% of Ehrlichia infections in the United States were reported from the states of Oklahoma, Missouri, and Arkansas. Infections are reported most commonly during the summer months, coincident with the adult and nymphal stages of the tick life cycle in which ticks are most likely to bite humans. Infections are also reported most commonly in the elderly. However, children are known to experience milder or subclinical infections and thus may be underrepresented in reporting.[4][5]

Pathophysiology

Infection with Ehrlichia species begins with the intracellular uptake of the infectious extracellular form of the organism, the elementary body (EB) or dense core (DC). The elementary body/dense core is then taken up by endocytosis, where the organism replicates and matures to form a reticulate body or reticulate core (RB/RC) and then morula before redifferentiating into elementary body/dense core that leaves the infected host cell to spread infection. During this process, Ehrlichia utilizes many immune evasion mechanisms including suppression of apoptosis of host cells, modulation of chemokine and cytokine responses and down-regulation of host pattern recognition receptors that might enable clearance of the infection. Ehrlichia preferentially infect peripheral blood leukocytes, with E. chaffeensis associated with human monocytic cells, including monocytes and macrophages, and neutrophil infections reported in E. ewingii. Multiorgan involvement is known to occur, with organisms detected in the spleen, lymph nodes, bone marrow and peripheral blood. The clinical manifestations of Ehrlichia infections are thought to be due to the host inflammatory response to the infection rather than direct damage from the bacteria.

History and Physical

Patients with Ehrlichia infections, regardless of organism, typically present with fever, malaise, headache, body aches, and chills. Symptoms typically begin one to two weeks after a tick bite, at a median of nine days. It is important to collect history regarding travel to endemic areas and outdoor activities of patients with these non-specific flu-like symptoms during the summer months, as prompt recognition and treatment of ehrlichiosis and other tick-borne illnesses may improve outcomes. Other findings may include gastrointestinal symptoms, such as nausea, vomiting and diarrhea, and rash. The rash is more common in children and typically presents five days into illness as a maculopapular rash, petechiae or diffuse erythema. A cough and respiratory symptoms are more common in adults than in children. Similar to rickettsial infections, central nervous system involvement can also occur in up to 20% of patients, including meningitis and meningoencephalitis. In some patients, symptoms may progress to acute respiratory distress syndrome (ARDS) or a sepsis-like or shock-like presentation with cardiovascular instability and coagulopathy. However, overall mortality is much lower in ehrlichiosis than in rickettsial disease. The Centers for Disease Control and Prevention (CDC) reports mortality rates of 1% to 3%, since 2000, in patients who present for medical care of ehrlichiosis. Importantly, many patients may be infected with ehrlichiosis but not present for medical evaluation, and thus this may be an overestimate of mortality. Patients who are immunocompromised, elderly, or have been pretreated with sulfonamide antibiotics are predisposed to more severe illness.[6][7][8][9]

Evaluation

Laboratory findings in ehrlichiosis may include leukopenia, thrombocytopenia, and mild to moderately elevated transaminases. Hyponatremia may also be observed. In some cases, morula may be observed in the peripheral blood or other body fluids of a patient with ehrlichiosis. However, this is not considered diagnostic of ehrlichiosis. cerebrospinal (CSF) leukocytosis and mildly elevated protein levels may also be observed. In most centers, diagnosis of ehrlichiosis occurs via polymerase chain reaction (PCR), which is particularly useful in these infections given their predilection for infecting circulating leukocytes. Treatment with doxycycline can decrease the sensitivity of PCR, so samples should be collected before initiation of treatment if possible without significantly delaying therapy. Serology may also be used; however, culture is not routinely performed to diagnose ehrlichiosis.

Treatment / Management

Doxycycline is the preferred drug for treatment of ehrlichiosis, as well as for rickettsial infection. There is no clinical data to support the use of alternative agents for ehrlichiosis, although in vitro studies suggest that rifampin may be an option. However, as there is no demonstrated clinical efficacy of rifampin in the treatment of ehrlichiosis and as rifampin has no efficacy against rickettsial infections, which can be indistinguishable from ehrlichiosis in the early stages of illness, doxycycline remains the drug of choice. Patients with ehrlichiosis typically defervesce in 48 to 72 hours after initiation of doxycycline. Treatment courses are typically five to seven days, based on illness severity. Several clinical studies have demonstrated that tooth staining is a rare cosmetic complication of doxycycline at the doses and duration used for the treatment of ehrlichiosis and rickettsial infections. Concerns regarding age and potential tooth staining should not delay treatment with doxycycline in children with suspected ehrlichiosis. There is currently no recommendation for post-tick bite prophylaxis against ehrlichiosis in endemic areas.[10][11]

Pearls and Other Issues

There is no vaccine available for any of the Ehrlichia species. Avoidance of tick bites remains the mainstay of prevention, with the application of insect repellents, avoidance of 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

The majority of patients with Ehrlichia infections present to the emergency department or to the primary care provider/nurse practitioner. Because the symptoms and signs of Ehrlichia infection are not specific, it is important to consult with an infectious disease expert early on. The infection can involve the skin, CNS, GI tract and muscle or even present with shock. The Centers for Disease Control and Prevention (CDC) reports mortality rates of 1% to 3%, since 2000, in patients who present for medical care of ehrlichiosis. Importantly, many patients may be infected with ehrlichiosis but not present for medical evaluation, and thus this may be an overestimate of mortality. Patients who are immunocompromised, elderly, or have been pretreated with sulfonamide antibiotics are predisposed to more severe illness

There is no vaccine available for any of the Ehrlichia species. Avoidance of tick bites remains the mainstay of prevention, with the application of insect repellents, avoidance of 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.[12][13]


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Ehrlichiosis - Questions

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An 8-year-old boy presents with fever, headache, leukopenia and body aches. He has no rash or skin lesions. He recently returned from a summer camping trip in Missouri. In addition to Rocky Mountain Spotted Fever, what other infection should be considered?



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Ehrlichiosis - References

References

Taira M,Ando S,Kawabata H,Fujita H,Kadosaka T,Sato H,Monma N,Ohashi N,Saijo M, Isolation and molecular detection of Ehrlichia species from ticks in western, central, and eastern Japan. Ticks and tick-borne diseases. 2019 Feb;     [PubMed]
Buzzard SL,Bissell BD,Thompson Bastin ML, Ehrlichiosis presenting as severe sepsis and meningoencephalitis in an immunocompetent adult. JMM case reports. 2018 Sep;     [PubMed]
Schwartz C,Katz DA,Larson M,Licciardi N,Kallick C,Kuzel TM, The relationship between ehrlichiosis and the development of hematologic malignancies. Medical hypotheses. 2018 Dec;     [PubMed]
Paulino 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;     [PubMed]
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;     [PubMed]
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.). 2018 Oct 17;     [PubMed]
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;     [PubMed]
Pujalte GGA,Marberry ST,Libertin CR, Tick-Borne Illnesses in the United States. Primary care. 2018 Sep;     [PubMed]
Eisen RJ,Eisen L, The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern. Trends in parasitology. 2018 Apr;     [PubMed]
Ismail N,McBride JW, Tick-Borne Emerging Infections: Ehrlichiosis and Anaplasmosis. Clinics in laboratory medicine. 2017 Jun;     [PubMed]
Saito TB,Walker DH, Ehrlichioses: An Important One Health Opportunity. Veterinary sciences. 2016 Aug 31;     [PubMed]
Buckingham SC, Tick-borne diseases of the USA: Ten things clinicians should know. The Journal of infection. 2015 Jun;     [PubMed]
McClure JC,Crothers ML,Schaefer JJ,Stanley PD,Needham GR,Ewing SA,Stich RW, Efficacy of a doxycycline treatment regimen initiated during three different phases of experimental ehrlichiosis. Antimicrobial agents and chemotherapy. 2010 Dec;     [PubMed]

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