Epidemiology of Human Ehrlichiosis
Human ehrlichiosis is a tick-borne illness that is caused by a very small type of bacteria known as "ehrlichiae." Human ehrlichiosis is just one member of a whole group of diseases known collectively as ehrlichioses, because each is caused by a different species of the genus Ehrlichia. Taxonomically, the Ehrlichiae are in the Order Rickettsiales, genus Ehrlichia. The ehrlichiae are very closely related to the rickettsiae, which are the type of bacteria that cause Rocky Mountain spotted fever (RMSF). The genus then breaks down further into a fairly large number of different species, each responsible for causing some form of ehrlichiosis, either in humans or some other mammalian species.
Ehrlichiae invade, and live within white blood cells, thereby adversely affecting the immune system and lessening the body's ability to fight secondary infections. They reside in the cytoplasm outside the nucleus. Ehrlichiae are pleomorphic, meaning variable in shape -- here you can see a number of individual ehrlichial organisms -- although they are generally considered to be more spherical or ellipsoidal in shape. They have a rippled outer cell wall, and an inner plasma membrane. Although ehrlichiae are sometimes scattered singly throughout the cytoplasm, they are most frequently found clustered together as aggregates of many organisms. These clusters are berry-like in appearance and are called "morulae."
Ehrlichiosis was first recognized in 1935, in Algeria, Africa, as a disease of dogs, otherwise known as canine ehrlichiosis. The pathogen was E. canis. The next major, related event was an outbreak of canine ehrlichiosis in military guard dogs stationed in Vietnam during the 1960s. This was very serious because a large number of dogs became ill and they all died due to hemorrhagic complications of the disease.
Ehrlichiosis in humans was first described in 1954 as a mononucleosis-like illness in Japan. This type of human ehrlichiosis is called Sennetsu fever and it occurs in limited areas of the Far East, primarily in Japan. It is extremely rare, usually very mild, and no deaths have ever been reported. It is caused by E. sennetsu.
For many years, Sennetsu fever was the only form of ehrlichiosis known to afflict humans. That is, until 1986 in this country, when a 51-year-old gentleman from Detroit became sick after being exposed to ticks in a rural area of Arkansas. From that time on, cases of human ehrlichiosis have been diagnosed on an annual basis, in many states, but primarily in the southeastern and south central states. At first, these human cases of ehrlichiosis were attributed to E. canis. But, finally, in 1990, Jacqueline Dawson and her colleagues at the Centers for Disease Control and Prevention (CDC) isolated a new species of Ehrlichia from the blood of a US Army reservist training at Fort Chaffee, Arkansas, and this new species of Ehrlichia was named E. chaffeensis. The specific form of human ehrlichiosis it causes was dubbed with the generic name 'human ehrlichiosis'. Which can be confusing if you're talking about different types of human ehrlichiosis.
Which brings us to what, most recently, appears to be yet another type of human ehrlichiosis, being called human granulocytic ehrlichiosis or HGE. The JAMA article reported on 12 cases that were treated at the Duluth Clinic in Minnesota, and they actually occurred during the period 1990 through 1993. What was of special concern about this revelation, is that it now appears that human ehrlichiosis is not limited to the southern United States, and may be quite serious since 2 out of the 12 patients died, despite treatment. Dr. Johan Bakken, one of the physicians at the Duluth Clinic, and senior author of the JAMA article, indicates that they have now seen a total of 32 cases of HGE and know of at least 15 more treated at other clinics throughout Minnesota and Wisconsin. The organism has not yet been isolated so we don't actually know if it's a new species of Ehrlichia or not. The major difference between human ehrlichiosis and HGE is the type of white blood cells that are infected. While E. chaffeensis invades non-granular white blood cells known as monocytes, the HGE organism is found in granulocytes, specifically neutrophils. The outward symptoms of both forms of human ehrlichiosis are the same.
Symptoms and Treatment
Symptoms of human ehrlichiosis begin approximately 1 week following infection and resemble those of RMSF, but usually without an accompanying rash. When a rash does appear (which it does in maybe 20-40% of cases), it tends to be more spotted in nature, but much less prominent than that seen in RMSF and more variable in appearance and location. Symptoms vary greatly in severity, ranging from an illness so mild that no medical attention is sought, to a severe, life-threatening condition. The most common early symptoms include high fever, headache, chills, and muscular aches and pains, which you can see mimic the early symptoms of many other tick-borne diseases. Consequently, human ehrlichiosis is often initially misdiagnosed. Of 185 cases that the CDC followed, most were initially diagnosed as RMSF or FUO (fever of unknown origin). In the most severe cases of human ehrlichiosis, respiratory or renal failure occurs. Prompt treatment with antibiotics is extremely important, and doxycycline is often very effective.
Through 1994 there have been approximately 390 cases of human ehrlichiosis recorded by the CDC, reported from 27 states. It is unclear what the true incidence of human ehrlichiosis is, however, because it is not a reportable disease. The CDC offers free testing of blood samples for a panel of 4 diseases: RMSF, Q Fever, typhus, and human ehrlichiosis. So, what they're calling the 'reported' cases are simply those cases where blood samples that happened to be submitted turned out to be positive. The current case definition that the CDC is using for human ehrlichiosis requires a 4-fold rise or fall in antibody titer.
The suspected vector for human ehrlichiosis, i.e., E. chaffeensis, is the Lone Star tick, because it is very prevalent across the southern United States where the majority of cases appear to have been acquired. It is less clear which tick species transmits the causative agent of HGE, but there have been reports of bites by the American dog tick (Dermacentor variabilis) and the black-legged tick (Ixodes scapularis) prior to onset of symptoms. The brown dog tick (Rhipicephalus sanguineus) is the most likely vector of canine ehrlichiosis.