Continuing Education Activity
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. This activity explains when this condition should be considered on a differential diagnosis, articulates how to properly evaluate for this condition, and highlights the role of the interprofessional team in caring for patients with this condition.
Objectives:
- Review the etiology of ehrlichiosis.
- Describe the presentation of ehrlichiosis.
- Summarize the treatment for ehrlichiosis.
- Outline the importance of enhancing care coordination among the interprofessional team to ensure proper evaluation and management of ehrlichiosis.
Introduction
The genus Ehrlichia consists of several species of obligate intracellular gram-negative bacteria that infect humans and various 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 associations 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 may be due to an increase in recognition and diagnostic availability as well as 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 the Centers for Disease Control and Prevention data, over 30% of reported Ehrlichia infections in the United States were 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, reports may underrepresent this population.[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 an elementary body/dense core that leaves the infected host cell to spread infection. During this process, Ehrlichia utilizes many immune evasion mechanisms, including suppressing 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 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 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. 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. 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 received pretreatment 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 a finding. In some cases, morulae may be present in the peripheral blood or other body fluids of a patient with ehrlichiosis. However, this is not considered a diagnostic of ehrlichiosis. Cerebrospinal leukocytosis and mildly elevated protein levels may also occur. 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 an option; however, culture is not a routine test performed to diagnose ehrlichiosis.
Treatment / Management
Doxycycline is the preferred drug for the 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 treating 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 to treat 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]
Differential Diagnosis
Prognosis
When diagnosed and treated promptly, ehrlichiosis will generally respond well, symptomatic improvement within 24 to 48 hours. However, in those with additional health conditions, severe infection, or who experience a delay in treatment, the disease can be serious or even fatal; this is why empiric therapy of suspected ehrlichiosis should commence immediately, even before the finalizing of laboratory results.[12]
Complications
In rare instances, e.g., patients with a weak immune system (as can be the case with HIV or cancer), ehrlichiosis can lead to serious complications. These include:
- Brain conditions, including confusion, seizures, or coma
- Hemorrhage
- Heart failure
- Respiratory failure
- Kidney failure
- Septic shock
These complications may require additional treatment, including respiratory support, IV fluids, or kidney dialysis. Complications are more prevalent in the elderly or people with pre-existing health conditions.[13]
Deterrence and Patient Education
Patients with ehrlichiosis cannot pass the disease on to other humans, but the presence of an infected individual indicates the potential for others to contract tick-borne diseases. Therefore patients need to be taught the best practices for tick avoidance as well as tick control measures.[14]
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 the primary care provider/nurse practitioner. Because the symptoms and signs of Ehrlichia infection are not specific, it is essential 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 received pretreatment 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.[15][16]
Ehrlichiosis