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Human Monocytic Ehrlichiosis (HME) is a rare infectious disease belonging to a group of diseases known as the Human Ehrlichioses. These diseases are caused by bacteria belonging to the "Ehrlichia" family. Several forms of Human Ehrlichioses have been identified, including Human Monocytic Ehrlichiosis, Sennetsu Fever, and Human Granulocytic Ehrlichiosis. Though caused by different strains of Ehrlichia bacteria, the disorders are characterized by similar symptoms.
The symptoms of Human Monocytic Ehrlichiosis may include a sudden high fever, headache, muscle aches (myalgia), chills, and a general feeling of weakness and fatigue (malaise) within a few weeks after initial infection. In addition, in many cases, laboratory findings may indicate an abnormally low number of circulating blood platelets (thrombocytopenia), a decrease in white blood cells (leukopenia), and an abnormal increase in the level of certain liver enzymes (hepatic transaminases). In some individuals, symptoms may progress to include nausea, vomiting, diarrhea, weight loss, and/or confusion. If HME is left untreated, life-threatening symptoms, such as kidney failure and respiratory insufficiency, may develop in some cases. Human Monocytic Ehrlichiosis is caused by the bacteria Ehrlichia chaffeensis (or E. chaffeensis). E. chaffeensis is carried and transmitted by certain ticks (vectors), such as the Lone Star tick (Amblyomma americanum) and the American dog tick (Dermacentor variabilis).
Human Monocytic Ehrlichiosis (HME) was the first form of Human Ehrlichial infection recognized in the United States. The onset of symptoms usually occurs about three weeks after an individual has been bitten by a tick carrying the bacterium Ehrlichia chaffeensis. Symptoms may initially include fever, chills, headaches, muscle pain (myalgia), and a general feeling of weakness and fatigue (malaise). In some cases, a rash may appear on the skin. Symptoms may then progress to include nausea, vomiting, loss of appetite (anorexia), and/or weight loss. Some affected individuals may also experience coughing, diarrhea, sore throat (pharyngitis), and pain in the abdominal area.
In most cases of HME, there is also an abnormal decrease in white blood cells (leukopenia), a low number of circulating blood platelets (thrombocytopenia), and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Some affected individuals may also experience inflammation of the liver (hepatitis).
In some severe cases of Human Monocytic Ehrlichiosis, if appropriate treatment is not received, symptoms may include shortness of breath (dyspnea); abnormalities in the blood's ability to clot properly (coagulopathy), potentially resulting in gastrointestinal bleeding; and/or neurologic abnormalities due to involvement of the brain and the spinal cord (central nervous system [CNS]). Affected individuals with CNS involvement may develop abnormal tissue changes (lesions) in the brain, experience inflammation of the protective membranes covering the brain and spinal cord (meningitis), and/or have abnormalities in the fluid surrounding the brain and spinal cord (cerebrospinal fluid). Neurologic symptoms and findings may include confusion, abnormal sensitivity to light (photophobia), stiffness of the neck, episodes of uncontrolled electrical disturbances in the brain (seizures), and/or coma. Additional neurologic abnormalities may include exaggerated reflex responses (hyperreflexia), impaired coordination of voluntary movements (ataxia), and/or loss of some motor function in the facial area due to impairment of one or more of the 12 nerve pairs arising from the brain (cranial nerve palsy). In severe cases, if HME is left untreated, life-threatening complications may result, such as kidney (renal) and/or respiratory failure.
Some affected individuals may have a milder form of Human Monocytic Ehrlichiosis, experiencing only some of the symptoms typically associated with the disorder. Such symptoms may include muscle aches (myalgia), joint pain (arthralgia), headache, and/or loss of appetite (anorexia). In addition, it is believed that some individuals affected with HME may demonstrate no obvious symptoms (asymptomatic).
The Human Ehrlichioses, including Human Monocytic Ehrlichiosis (HME), are caused by bacteria belonging to the "Ehrlichia" family. They are considered "gram-negative" bacteria. Bacteria may be considered "gram negative" or "gram positive," depending upon the results of "Gram's stain," a testing method in which bacteria are stained with various solutions to help identify and classify the bacteria. Such staining may be essential in identifying a specific bacterium responsible for an infectious disorder and determining appropriate, effective treatments.
In most cases, it is believed that Human Ehrlichial infection results from tick bites. Certain types of ticks serve as "vectors," carrying and then transmitting the Ehrlichia bacteria to humans. A vector is any organism that is infected with a particular disease agent (e.g., bacterium or virus), carries it, and later transmits it to another organism, which may then become infected by the disease agent in question.
Human Monocytic Ehrlichiosis is caused by a bacterium named Ehrlichia chaffeensis (or E. chaffeensis). E. chaffeensis is transmitted by tick vectors, such as the Lone Star tick (Amblyomma americanum) and the American dog tick (Dermacentor variabilis). The genetic composition of E. chaffeensis is closely related to that of two other types of Ehrlichia bacteria, i.e., Ehrlichia canis and Ehrlichia ewingii. Both of these Ehrlichial bacteria are known to cause Ehrlichiosis in dogs. In addition, the E. ewingii bacterium has been found to cause a newly recognized form of Human Ehrlichiosis. (For more information, please see the "Related Disorders" section below.)
In Human Monocytic Ehrlichiosis, the Ehrlichial bacterium (E. chaffeensis) spreads through blood and lymphatic vessels. Lymph, a body fluid, carries cells that help fight infection. E. chaffeensis then invades certain cells (monocytes and macrophages) that play an essential role in the body's immune system by engulfing and digesting microorganisms (phagocytosis), such as bacteria and other foreign materials. The invading Ehrlichial bacteria grow within membrane-bound cavities (vacuoles) in monocytes and macrophages in the blood and certain body tissues (e.g., bone marrow, lymph nodes, liver, spleen, kidneys, lungs, and the fluid that surrounds the brain and spinal cord [cerebrospinal fluid]).
Human Monocytic Ehrlichiosis was first recognized in the United States in 1986. At that time, a male who was approximately 50 years of age was bitten by a tick in Arkansas. He experienced the symptoms of Ehrlichial infection approximately two weeks after tick exposure. Studies were later conducted by the Centers for Disease Control (CDC) and state public health officials, demonstrating that many individuals in the United States who had originally been diagnosed with Rocky Mountain Spotted Fever or a related disorder may have actually experienced Human Ehrlichial infection. In 1991, when a soldier stationed at an army base in Arkansas experienced similar symptoms, the bacterium responsible for the infection was isolated. The bacterium, named "Ehrlichia chaffeensis" after the army base where the soldier was stationed (Fort Chaffee, Arkansas), is the cause of Human Monocytic Ehrlichiosis (HME).
From 1986 to 1997, 742 cases of HME were reported to the CDC. Most cases have occurred in the mid-Atlantic and southeastern states in the United States, although some have been reported from other states, including Washington, Wyoming, and Utah, as well as other continents, including Europe and Africa. However, because some individuals with HME may demonstrate no obvious symptoms (asymptomatic), it may be difficult to determine the true frequency of this form of Human Ehrlichiosis in the general population.
HME infection most commonly occurs in rural areas in the months of May, June, and July. In theory, this disease affects males and females in equal numbers. However, in observed cases, approximately 80 percent of affected individuals are male, while about 20 percent are female. Infection tends to occur when individuals participate in recreational or occupational activities that expose them to tick vectors.
Researchers believe that the distinct geographic distributions of the Human Ehrlichioses may result from differences in the distribution of the various vectors (e.g., raw fish, Lone Star tick, American dog tick, deer tick) carrying and transmitting the different Ehrlichia bacterial strains.
A recent report by the Centers for Disease Control and Prevention suggests that the incidence of both HME and Human Granulocytic Ehrlichiosis is underreported.
Symptoms of the following disorders may be similar to those of Human Monocytic Ehrlichiosis (HME). Comparisons may be useful for a differential diagnosis:
Human Granulocytic Ehrlichiosis (HGE), a rare infectious disease, is caused by a bacterium from the "Ehrlichia" family that has not yet been named. The bacterium, which is carried and transmitted by ticks (vectors), invades certain granular white blood cells (neutrophils) that play a role in engulfing bacteria, removing them from the blood, and destroying them (phagocytosis). In individuals with HGE, the onset of symptoms usually occurs approximately one week after an individual has been bitten by a tick carrying the Ehrlichia bacterium. In almost all cases, symptoms include fever, chills, muscle pain (myalgia), a general feeling of weakness and fatigue (malaise), and/or headaches. Some affected individuals may also experience coughing, nausea, vomiting, and/or confusion. In addition, in many cases, certain abnormal laboratory findings may occur including an abnormal increase in the level of certain liver enzymes (hepatic transaminases), an abnormal decrease in circulating blood platelets (thrombocytopenia), anemia, and/or a decrease in certain white blood cells (granulocytopenia). In some severe cases, if Human Granulocytic Ehrlichiosis is left untreated, life-threatening symptoms, such as kidney failure and respiratory insufficiency, may result. Most cases have affected individuals in the Northeastern and Midwestern United States. (For more information on this disorder, choose "Human Granulocytic Ehrlichiosis" as your search term in the Rare Disease Database.)
Sennetsu Fever, a rare infectious disease that also belongs to the Human Ehrlichioses, is caused by the bacterium known as Ehrlichia sennetsu. The symptoms of Sennetsu Fever may include a sudden high fever, headache, and muscle aches (myalgia) within a few weeks after initial infection. Some affected individuals may also experience nausea, vomiting, and/or loss of appetite (anorexia). In addition, in many cases, abnormal laboratory findings may occur including a decrease in white blood cells (leukopenia) and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). The vector (or carrier) for the E. sennetsu bacterium has not yet been determined; however, some researchers believe that infection may result from ingestion of raw fish. Reported cases of Sennetsu Fever appear to be limited to Western Japan and Malaysia. (For more information on this disease, choose "Sennetsu" as your search term in the Rare Disease Database.)
The most recently identified form of Human Ehrlichiosis has been reported in four individuals in Missouri, all of whom experienced tick exposure several days prior to symptom onset. Based upon certain specialized laboratory tests, the four individuals tested positive for Ehrlichial infection yet negative for all known human forms of the disease (e.g., HME, HGE). Further tests revealed that the infection was caused by Ehrlichia ewingii, a bacterium that was previously thought only to cause Ehrlichial infection in dogs (Canine Granulocytic Ehrlichiosis). The researchers indicated that there is no evidence of direct disease transmission from dogs to humans. Rather, humans and dogs both appear to be hosts to the same tick vectors. Associated symptoms typically include fever, headache, joint and muscle pain, and a general feeling of ill health (malaise). In addition, as with other forms of Human Ehrlichiosis, abnormal laboratory findings may also be present, such as abnormally low levels of circulating platelets (thrombocytopenia) and a decrease in the level of white blood cells (leukopenia). Three of the four individuals with this form of Ehrlichiosis had been receiving therapy with medications that suppress the activities of the immune system (immunosuppressants). It is unclear whether infection with the E. ewingii bacterium usually does not affect individuals with sufficient immune system functioning (immunocompetence) or results in mild or no apparent symptoms (asymptomatic) in such cases. Therefore, the implications of such findings are not yet understood. All individuals with this form of Human Ehrlichiosis responded to treatment with the antibiotic doxycycline. (For more information on Human Ehrlichiosis treatment, please see the "Standard Therapies" section of this report below.)
Lyme Disease is an infectious disorder caused by the spirochete bacterium Borrelia burgdorferi. The bacterium is carried and transmitted by deer ticks (Ixodes dammini). In most cases, Lyme Disease is first characterized by the appearance of a red skin lesion (erythema chronicum migrans), which begins as a small elevated round spot (papule) that expands to at least five centimeters in diameter. Symptoms may then progress to include low-grade fever, chills, muscle aches (myalgia), headache, a general feeling of weakness and fatigue (malaise), and/or pain and stiffness of the large joints (infectious arthritis), especially in the knees. Such symptoms may tend to occur in recurrent cycles. In severe cases, heart muscle (myocardial) and/or neurologic abnormalities may occur. Most cases of Lyme Disease occur in the northeastern United States. However, cases have occurred in other areas of the U.S. as well as other countries including China, Japan, Australia, and several countries in Europe. (For more information on this disorder, choose "Lyme" as your search term in the Rare Disease Database.)
Babesiosis is a group of infectious diseases caused by single-celled microorganisms (protozoa) belonging to the "Babesia" family. It is believed that the Babesia protozoa are usually carried and transmitted by ticks (vectors). Babesiosis occurs primarily in animals; however, in rare cases, Babesiosis infection may occur in humans. Certain Babesia species are known to cause Babesiosis infection in humans (i.e., Babesia microti), and the deer tick (Ixodes dammini) is a known vector. Human Babesiosis infection may cause fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia). Additional features may include premature destruction of red blood cells (hemolytic anemia), an abnormal decrease in circulating blood platelets (thrombocytopenia) and white blood cells (leukopenia), and/or an enlarged spleen (splenomegaly). Symptoms may be mild in otherwise healthy people; some infected individuals may exhibit no symptoms (asymptomatic). A severe form of Babesiosis, which can be life-threatening if untreated, can occur in people who have had their spleens removed (splenectomized) or who have an impaired immune system. In the United States, Babesiosis is most common in the northeastern states. In rare cases, Babesiosis may occur in Europe. (For more information on this disorder, choose "Babesiosis" as your search term in the Rare Disease Database.)
Rocky Mountain Spotted Fever is a rare infectious disorder caused by the bacterium Rickettsia rickettsii. The bacterium is carried and transmitted by tick vectors, such as the Lone Star tick (Amblyomma americanum) and the American dog tick (Dermacentor variabilis), which are also known vectors for Human Monocytic Ehrlichiosis. Rocky Mountain Spotted Fever is characterized by severe headache, high fever, chills, muscle aches (myalgia), and/or confusion. In most cases, a skin rash may appear approximately two to six days after tick exposure; the rash may first appear on the palms, wrists, soles, ankles, and forearms, later spreading to the face, trunk, and lower arms and legs. Some affected individuals may also experience nausea, vomiting, and/or abdominal pain. In some cases, without early diagnosis and appropriate treatment, symptoms may become life-threatening. Rocky Mountain Spotted Fever characteristically occurs in outbreaks in various areas of the Midwestern, Eastern, and Southeastern United States. (For more information on this disorder, choose "Rocky Mountain Spotted Fever" as your search term in the Rare Disease Database.)
Meningococcal disease is an infectious disease caused by the bacterium Neisseria meningitidis in the bloodstream. The symptoms associated with meningococcal disease may vary greatly from case to case, with associated findings ranging from a short fever and upper respiratory illness to sudden, severe infection with potentially life-threatening complications. In some cases, affected individuals may progress from one manifestation to another. In some individuals with meningococcal disease, symptoms may include fever, chills, headache, generalized weakness, a general feeling of ill health (malaise), and/or low blood pressure (hypotension). Many affected individuals may also have areas of abnormal bleeding (hemorrhage) within skin layers, causing the appearance of small purplish spots on the skin (petechia). In addition, in those with meningococcal disease, laboratory findings may include abnormally elevated levels of white cells in the blood (lymphocytosis). In some severe cases, affected individuals may experience inflammation of the protective membranes covering the brain and spinal cord (meningococcal meningitis). Associated symptoms may include the sudden onset of severe fever, chills, nausea, vomiting, and/or stiff neck, followed by confusion, drowsiness, and loss of consciousness. In such cases, life-threatening complications may result without immediate, appropriate treatment. (For more information on this disease, choose "Meningococcemia" or "Meningitis, Meningococcal" as your search term in the Rare Disease Database.)
There are other infectious disorders that may be characterized by sudden high fever (febrile disorders), headache, myalgia, nausea, vomiting, thrombocytopenia, leukopenia, and/or other symptoms associated with Human Monocytic Ehrlichiosis. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
Human Monocytic Ehrlichiosis (HME) may be diagnosed based upon a thorough clinical evaluation, characteristic findings, and specialized laboratory tests. Blood tests may reveal findings often associated with the Human Ehrlichioses such as abnormally low levels of blood platelets (thrombocytopenia), low levels of certain white blood cells (leukopenia), and/or elevated levels of certain liver enzymes (such as aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). In some cases, laboratory tests may reveal abnormalities of the cerebrospinal fluid. In addition, chest X-rays may reveal abnormalities in the lungs (e.g., pulmonary infiltrates, increased fluid in the lungs).
Examination of blood smears under a microscope that uses an electron beam (electron microscopy) may reveal clusters of bacteria in membrane-bound cavities (vacuoles) within certain cells (e.g., monocytes); however, such clusters may not be apparent early in the course of infection. In some cases, additional specialized laboratory tests may then be conducted to help determine and/or to confirm a diagnosis of a specific bacterial infection.
Specialized laboratory tests may include Indirect Immunofluorescence Assays (IFA) conducted on the fluid portion of an affected individual's blood (serum). Antibodies, which are proteins manufactured by certain white blood cells, help the body fight toxins and invading microorganisms. In Indirect Immunofluorescence Assays, human antibodies are marked with special fluorescent dyes and a microscope with ultraviolet light is used, enabling researchers to observe antibody response to certain microorganisms.
IFA testing has been used in confirming a diagnosis of all known types of Human Ehrlichial infection. However, in Human Monocytic Ehrlichiosis (HME), the bacterium responsible for the infection (Ehrlichia chaffeensis) was not characterized and identified (isolated) until 1991. Therefore, for many years, HME infection was diagnosed by observing the antibody response in a patient's blood serum to the bacterium responsible for Canine Ehrlichiosis, Ehrlichia canis, a bacterium that is very genetically similar to E. chaffeensis. Since E. chaffeensis was isolated in 1991, cases of HME have been confirmed by IFA testing that measures antibody response either to E. chaffeensis itself or the closely-related E. canis.
Measurable diagnostic rises in antibody response to the Ehrlichia bacteria may not occur until approximately three weeks after the onset of Human Monocytic Ehrlichiosis. As a result, initial IFA blood serum results may be negative in some cases. Therefore, more sensitive testing techniques that can help establish early diagnosis may be used in some cases.
One such process, called Polymerase Chain Reaction (PCR), is a laboratory technique in which sequences of DNA (which contains the organism's genetic information) can be copied over and over again quickly. This enables close analysis of the DNA, aiding in the identification of the organism in question. PCR conducted on certain bacterial DNA sequences obtained from patients' blood samples may confirm Human Ehrlichial infection due to a particular strain of Ehrlichia. PCR has been used to establish an early diagnosis of Human Ehrlichial infection in some cases of HME.
The information in the medical literature indicates that because it may be difficult to differentiate Human Ehrlichial infection, such as Human Monocytic Ehrlichiosis, from other illnesses that are also characterized by high fever (febrile illnesses), Ehrlichiosis should be considered in any patient with high fever, thrombocytopenia, and leukopenia who has recently been exposed to ticks. In addition, HME should be considered in individuals with high fever, severe headache, and neurologic symptoms, particularly in areas where HME infection is known to occur and during peak seasons for such infection.
If HME is suspected, treatment should not be delayed until diagnosis has been confirmed by IFA testing, since a positive antibody response may not occur until several weeks after initial infection. Therapy should begin as soon as possible after the onset of symptoms.
The treatment of Human Monocytic Ehrlichiosis usually entails standard doses of tetracycline antibiotics. Alternatively, doxycycline therapy may be administered. In severe cases of HME infection, hospitalization may be required. Other treatment is symptomatic and supportive.
Individuals in geographic areas who risk exposure to tick vectors for Ehrlichial infection should consider taking certain steps to prevent infection. Such steps should include wearing long-sleeved shirts, long pants, and hats; wearing light-colored clothing to make ticks more visible; using insect repellents; and carefully checking their clothing and skin (particularly the scalp and the back of the neck) after being in fields or wooded areas.
Initial laboratory (in vitro) studies have shown that the bacterium that causes Human Monocytic Ehrlichiosis (E. chaffeensis) may be susceptible to the antibacterial drug rifampin. Further research is needed to determine whether rifampin would be a safe, effective therapy in the treatment of HME.
Ongoing studies are underway to determine the geographic distribution of different forms of Human Ehrlichial infection; examine whether infection with one Ehrlichia bacterial strain may result in immunity to other strains; and determine the occurrence rates of Human Ehrlichial infection among those who do not exhibit obvious symptoms (asymptomatic infection).
Research on tropical and other infectious diseases such as the Human Ehrlichioses is ongoing. For more information about these disorders, please contact the World Health Organization (WHO) listed in the Resources section below.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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Report last updated: 2009/04/07 00:00:00 GMT+0