Ehrlichia and Anaplasma

Definitions & Key takeaways

Ehrlichia and Anaplasma are bacteria that are transmitted by ticks. Ehrlichia causes ehrlichiosis, whereas Anaplasma causes anaplasmosis. Ehrlichiosis and Ehrlichiosis present with similar symptoms, which include headache, fever, muscle pain, nausea and vomiting. Most people who get infected with these bacteria do not have any symptoms, but in some cases these bacteria can cause serious illness. Ehrlichiosis and Ehrlichiosis are diagnosed with PCR or serology tests, and are treated with antibiotics.

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Ehrlichia and Anaplasma are two genera of Gram-negative pleomorphic bacteria, which means they can take different shapes - round like a coccus, or coccobacillary, which means somewhere between a spherical coccus and a rod-like bacillus.
The most common species that cause disease in humans are Ehrlichia chaffeensis, which causes a disease called human monocytic ehrlichiosis, or HME, and Anaplasma phagocytophilum, which causes a disease called human granulocytic anaplasmosis, or HGA.
Now, Ehrlichia and Anaplasma have a thin peptidoglycan layer, so they don’t retain the crystal violet dye during Gram staining.
Instead, like any other Gram-negative bacteria, they stain pink with safranin dye. Both are non-motile, non-spore forming, and obligate intracellular which means they can survive only inside cells.Finally, Ehrlichia and Anaplasma don’t grow on routine culture media and they need to be cultivated in vitro in different cell lines.
So, Ehrlichia chaffeensis can be isolated in DH82 canine histiocytic cell line and Anaplasma phagocytophilum can be isolated in promyelocytic leukemia HL-60 cell line.Now, Ehrlichia and Anaplasma enter circulation following a tick bite and once inside the body, they infect circulating leukocytes.
Ehrlichia primarily targets monocytes and macrophages, and it infects them using tandem repeat proteins, or TRP. These bacterial proteins bind to proteins found on the surface of the cell, and they induce phagocytosis - so basically, they make the cell gobble up the bacteria.
Anaplasma, on the other hand, primarily targets neutrophils, and infects them with the help of a P-selectin glycoprotein which binds on the P-selectin glycoprotein ligand-1, or PSGL-1 found on the surface of neutrophils.
This activates an intracellular pathway that leads to reorganization of cellular actin which leads to phagocytosis, allowing Anaplasma to enter the cell.Once inside the cell, both Ehrlichia and Anaplasma live in an early endosome, which normally merge with lysosomes to kill invading bacteria.
But, in order to merge with lysosomes, this early endosome needs to become a late endosome. So, the early endosome contains a protein called rab5A, which is involved in the recruitment of rab7A and the maturation of these compartments into late endosomes.
However, Ehrlichia and Anaplasma don’t let that happen, so it stops the production of rab5A. How they do that is still unknown, but the end result is that the early endosome can’t become a late endosome, so it doesn’t merge with the lysosome.
Thus, bacteria avoid intracellular killing by lysosomal enzymes. Additionally, Anaplasma can avoid intracellular killing by inhibiting the production of reactive oxygen species produced by neutrophils to destroy invading bacteria.
Also, it has the ability to destroy XIAP, a protein which normally inhibits neutrophil apoptosis, or programmed cell death.
So, by destroying XIAP, it stimulates neutrophil death. Now, when they are safe from intracellular killing, Ehrlichia and Anaplasma replicate inside early endosomes by binary fission.
This means the bacteria split in two identical copies - and if it sounds similar to mitosis...well, it is! But the term binary fission is used to describe division of prokaryotic cells, which don’t have a nucleus, and therefore some steps in replication are different from mitosis.
So, they form microcolonies inside endosomes, called morulae, which are mulberry-like inclusions. Finally, when they replicated enough they cause cell lysis leading to release of bacteria into the bloodstream and from there they can disseminate into multiple organs such as the lungs, heart, kidneys, liver or central nervous system.
So both Ehrlichia and Anaplasma can cause serious complications if left untreated, such as respiratory failure, heart failure, renal failure and septic shock.
Neurological complications associated with Ehrlichia infections are mainly meningitis and meningoencephalitis, while for Anaplasma, complications include demyelinating polyneuropathy, when the myelin sheath of neurons in the upper and lower limbs is destroyed, resulting in nerve damage, and brachial plexopathy, which is when there is damage to the brachial plexus, where upper limb nerves originate.Now, Ehrlichia is transmitted by Amblyomma americanum, or the lone star tick which is usually found in northeastern and midwestern US.
On the other hand, Anaplasma is transmitted by Ixodes tick found in deer and white-footed mice. There are three types of Ixodes ticks involved in the transmission of Anaplasma: Ixodes pacificus found in western US, Ixodes ricinus found in Europe, and Ixodes scapularis found in eastern US.
On a side note, Ixodes scapularis can also transmit Borrelia burgdorferi, which causes Lyme disease, as well as Babesia species, which cause babesiosis - so coinfections are possible.
Symptoms of both human monocytic ehrlichiosis and human granulocytic anaplasmosis include fever, chills, severe headache, myalgias, nausea, vomiting and loss of appetite.
There’s also an atypical rash that looks like red splotches or pinpoint dots located on trunk, but it spares the hands and feet.
With meningitis and meningoencephalitis there may be fever, headache, stiff neck, confusion, hallucinations and seizures.
With demyelinating polyneuropathy there is tingling or numbness in the toes and fingers, weakness of the arms and legs, fatigue and abnormal sensations, and with brachial plexopathy there may be numbness, pain and weakness of the shoulder, arm or hand.Diagnosis is done with a peripheral blood sample that identifies the characteristic morulae in monocytes and neutrophils using Wright stain.
PCR can also be done to identify bacterial DNA. Serological tests, like indirect immunofluorescence assay, or IFA, can be done to detect IgM and IgG antibodies against Anaplasma or Ehrlichia.
Routine lab studies can show leukopenia, thrombocytopenia, anemia, hyponatremia, or low concentrations of sodium in the blood, mildly or moderately elevated hepatic transaminase levels.
When there’s central nervous system involvement, a cerebrospinal fluid analysis can be done, which can identify the morulae.
Finally, treatment is done with antibiotics such as doxycycline, as the first drug of choice, or chloramphenicol, as an alternative.##SummaryAlright, as a quick recap.
Ehrlichia and Anaplasma are tick-borne, gram-negative pleomorphic bacteria, non-motile, non-spore forming and obligate intracellular.
Ehrlichia infects monocytes and macrophages leading to a disease called human monocytic ehrlichiosis, or HME and Anaplasma infects neutrophils leading to a disease called human granulocytic anaplasmosis, or HGA.
Diagnosis is done by identifying in a peripheral blood smear the characteristic morulae found in monocytes and neutrophils using Wright stain, with PCR which can identify bacterial DNA and with serological tests such as IFA.
Treatment is done with doxycycline, as the first drug of choice, or chloramphenicol, as an alternative.