Ehrlichia chaffeensis is an obligately intracellular, Gram-negative species of Rickettsiales bacteria. It is a zoonotic pathogen transmitted to humans by the lone star tick (Amblyomma americanum).
It is the causative agent of human monocytic ehrlichiosis.
Human monocytic ehrlichiosis caused by E. chaffeensis is known to spread through tick infection primarily in the Southern, South-central and Mid-Atlantic regions of the United States. In recent years, the lone star tick has expanded its range along the East Coast to New England, putting more humans at risk for tick-borne infections.Little, S. E. (2007, January). New developments in managing vector-borne diseases. Retrieved from http://www.iknowledgenow.com/tocnavc2007smallanimal.cfm
It is named for Fort Chaffee, where the bacterium was first discovered in the blood sample of an infected patient in 1986.
Epidemiology
Transmission cycle
E. chaffeensis is maintained in nature through a complex zoonotic relationship. The white-tailed deer (Odocoileus virginianus) is known to be the main competent reservoir for E. chaffeensis and the lone star tick (Amblyomma americanum) is the principal vector for human transmission. Some evidence shows that other organisms may serve as reservoirs for the bacteria such as domestic goats, domestic dogs, raccoons, and coyotes.
E. chaffeensis can be transmitted to uninfected tick larvae when feeding on the blood from an infected host. The infection is then maintained and can be transmitted to a reservoir organism or humans at the nymphal stage. Adult ticks can maintain the infection or be infected from feeding on the blood of an infected reservoir organism and may also pass E. chaffeensis to humans or other uninfected reservoir organisms. Transovarial transmission is not known to occur, so eggs and unfed larvae are not believed to be infected.
Experimental studies in the related species Ehrlichia japonica have suggested that the conserved effector TRP120 promotes sustained bacteremia needed for efficient tick acquisition, providing a possible molecular explanation for maintenance of the tick–mammal transmission cycle in Ehrlichia.
The seroprevalence of E. chaffeensis ranges from 0.4-12.5% in endemic regions, and approximately 75% of seroconversions are subclinical.
Microbiology All members of the genus Ehrlichia are obligate intracellular bacteria, being closely related to the genera Rickettsia and Orientia. Taxonomic classification largely relies on the sequencing of the 16S rRNA genes and the heat shock operon.
The small dense core form (approximately 0.2-0.4 micrometers) of intracytoplasmic clusters of E. chaffeensis found inside of infected cells resemble elementary bodies of Chlamydia spp., the larger form (0.6-1.5 micrometers) resemble reticulate bodies. A few days post infection, the elementary bodies form an inclusion called a morula, which can then be seen microscopically. Eventual cell lysis allows for the release of bacteria, which can then infect new cells.
In contrast to the reductive evolution commonly seen in other intracellular bacteria, many pseudo genes are present in the Ehrlichia genus, including E. chaffeensis, demonstrating potential gene duplication events. The duplication of the tandemly repeated sequences is likely to result in new genes, antigenic variation, immune evasion, thus supporting enhanced survival.
E. chaffeensis has been isolated from peripheral blood by direct inoculation of leukocyte fractions or whole blood into flasks containing adherent cells; the most commonly used cell in successful isolation is the canine histiocytic cell line DH82, however, a wide variety of cells have been used for primary isolation, including the human macrophage like THP-1 cells, the fibroblast-like HEL-22 cells, Vero cells, and HL-60 cells. Growth is enhanced by incubation with rocking at 37°C in 5% CO2. Even so, culture may take up to one month, although growth has been achieved in just a few days. Culture is slightly more sensitive than direct peripheral blood observation, thus E. chaffeensis could be isolated even when infected leukocytes are not initially observed.
Pathogenesis
E. chaffeensis causes human monocytic ehrlichiosis and is known to infect monocytes. It has also been known to infect other cell types such as lymphocytes, atypical lymphocytes, myelocytes, and neutrophils, but monocytes appear to best harbor the infection.
E. chaffeensis enters leukocytes by binding EtpE, an outer-membrane invasin unique to the bacterium, to the outer membrane of the host cell. A cell surface protein called DNase X is used as a receptor for the invasin protein.
E. chaffeensis has also been shown to infect canines both naturally and artificially.Baneth, G. (2010). Ehrlichia and anaplasma infections. Paper presented at World small animal veterinary congress. Retrieved from http://www.ivis.org/proceedings/wsava/2010/d12.pdf Symptoms in canine infections are hard to differentiate between E. chaffeensis infection and E. canis, which is the species of Ehrlichia that most commonly affects canines.
Signs and symptoms Infection with Ehrlichia chaffeensis causes human monocytic ehrlichiosis. Symptoms typically develop within 1 to 2 weeks after exposure, with the median incubation period of approximately 9 days. Early symptoms commonly include fever, headache, malaise, myalgia, nausea and arthralgia. Low-back pain and. other gastrointestinal symptoms may also occur. As the illness progresses, approximately 10–40% of patients develop additional symptoms including coughing, pharyngitis, diarrhea, vomiting, abdominal pain, or changes in mental status. Patients commonly seek medical attention within 3-4 days after the onset of symptoms.
As the course of infection continues, petechial, macular, and maculopapular rashes may occur with varied distribution and onset. Rashes are most common in children, occurring in 67% of pediatric cases. Among adult patients, majority of rash presentation is in correlation with HIV infection.
Fulminant infections are more common in patients immunocompromised by HIV, immunosuppressive treatments, monoclonal gammopathy, asplenia, sickle β-thalassemia, or Down's syndrome. Among this immunocompromised population, symptom severity usually correlates with the level of E. chaffeensis in the blood. However, this finding is not true for every case.
Ehrlichiosis has the possibility to be fatal without proper treatment, leading diagnosis to be important. However, symptoms are non-specific and can easily be misdiagnosed. Documented tick-exposure can increase the likelihood of correct diagnosis and prompt care. The length of time between disease development and treatment directly correlates with the risk of symptoms requiring ICU care.
Overall case fatality is 2-3%, but male sex, advanced age, and an immunocompromised status have been associated with a higher mortality.
Diagnosis and detection
There are three primary methods in diagnosing E. chaffeensis infection: PCR amplification of nucleic acids, detection of morulae in the cytoplasm of infected leukocytes by nonspecific Romanowsky stains (such as Giemsa or Wright) or immunocytologic/immunohistologic stains using antibodies against E. chaffeensis, or by culture of blood or cerebrospinal fluid. The ideal specimen is EDTA-anticoagulated blood, as it can be used for most tests, and should be obtained during the active phase of illness.
In culture, the presence of infected cells is demonstrated by sampling some of the cell containing medium, or by scraping a part of the monolayer, then centrifuging the sample. Staining with Romanowsky or immunofluorescent stains will demonstrate the presence of intra-cytoplasmic morulae or E. chaffeensis antigen, depending on the stain used.
Treatment E. chaffeensis is susceptible to tetracyclines. Doxycycline is the treatment of choice for suspected human monocytotropic ehrlichiosis in adults and children of all ages, and treatment should be started as soon as the disease is suspected rather than delayed pending laboratory confirmation. Patients are typically treated for at least 5 to 7 days and until 72 hours after fever has resolved with evidence of clinical improvement.
See also Ehrlichiosis
References