Sennetsu Fever

Disease Overview

Sennetsu Fever 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 Ehrlichial infection have been identified including Sennetsu Fever, Human Monocytic Ehrlichiosis (HME), and Human Granulocytic Ehrlichiosis (HGE). Though caused by different strains of Ehrlichia bacteria, the disorders are all characterized by similar symptoms.

The symptoms of Sennetsu Fever may include a sudden high fever, headache, and muscle aches (myalgia) within a few weeks after initial infection. In some cases, affected individuals may also experience nausea, vomiting, and/or loss of appetite (anorexia). In addition, in many cases, abnormal laboratory findings may include a decrease in white blood cells (leukopenia) and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Sennetsu Fever is caused by the bacterium Ehrlichia sennetsu. The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish.

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Synonyms

• Human Ehrlichial Infection
• Human Ehrlichial Infection
• Human Ehrlichial Infection, Sennetsu Type
• Sennetsu Type

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Signs & Symptoms

The symptoms of Sennetsu Fever, the first recognized form of Human Ehrlichiosis, tend to begin approximately two weeks after an individual has been infected with the bacterium Ehrlichia sennetsu. Affected individuals may then experience severe headaches, muscle aches (myalgia), sudden fever, chills, swollen lymph nodes (lymphadenopathy), nausea, vomiting, and/or loss of appetite (anorexia). In very rare cases, a rash may appear on the skin.

In the beginning of the illness, affected individuals may exhibit an abnormal decrease in the number of circulating white blood cells (leukopenia); later in the course of the infection, there may be an abnormal increase in the production of certain white blood cells (lymphocytosis) as the body’s immune system works to fight the infection. Individuals with Sennetsu Fever may also exhibit an abnormally enlarged liver and spleen (hepatosplenomegaly) and a mild to moderate increase in the level of certain liver enzymes (hepatic transaminases).

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Causes

The Human Ehrlichioses, including Sennetsu Fever, are caused by bacteria belonging to the “Ehrlichia” family. They are considered “gram-negative” bacteria. Bacteria may be classified as “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.

Sennetsu Fever is caused by a bacterium called Ehrlichia sennetsu (or E. sennetsu). The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish. 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. The genetic makeup of the bacterium E. sennetsu is closely related to that of a bacterium called Ehrlichia risticii, which causes an Ehrlichial infection in horses (Potomac Horse Fever).

In Sennetsu Fever, the Ehrlichial bacterium (E. sennetsu) spreads through blood and lymphatic vessels. Lymph, a body fluid, carries cells that help fight infection. E. sennetsu then invades certain cells (monocytes and macrophages). These are large cells (mononuclear phagocytes) 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]).

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Affected populations

The Ehrlichioses are a group of rare infectious diseases caused by members of the “Ehrlichia” bacteria family. Until recently, the Ehrlichioses were known primarily as veterinary disorders. Since the early 1900s, several forms of veterinary Ehrlichioses have been identified, each caused by a different strain of Ehrlichia; in most cases, the bacteria are transmitted by ticks (vectors). Veterinary Ehrlichial infections have been identified that cause disease in horses, sheep, deer, cattle, rodents, and/or dogs. For example, a form of Ehrlichial infection in dogs was first identified in Algeria in 1935 (Canine Ehrlichiosis). The disorder is now a well-recognized canine disease across the world; it is most common in subtropical and tropical areas.

In rare cases, Ehrlichiosis may affect humans. The first recognized form of Human Ehrlichial infection, Sennetsu Fever, was identified in Japan in 1954. Reported cases of Sennetsu Fever appear to be limited to Western Japan and Malaysia.

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.

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Disorders with Similar Symptoms

Symptoms of the following disorders may be similar to those of Sennetsu Fever. 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). The invading bacteria grow within membrane-bound cavities (vacuoles) in the neutrophils in circulating blood. 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), 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 increase in the level of certain liver enzymes (hepatic transaminases), low levels of 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.)

Human Monocytic Ehrlichiosis (HME) is a rare infectious disease caused by a bacterium from the “Ehrlichia” family known as Ehrlichia chaffeensis. The invading bacteria spread through blood and lymphatic vessels and invade certain cells that play an essential role in the body’s immune system (monocytes and macrophages). In individuals with HME, the onset of symptoms usually occurs about three weeks after an individual has been bitten by a tick carrying the E. chaffeensis bacterium. 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), pain in the abdominal area, and/or confusion. In many 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 exhibit inflammation of the liver (hepatitis). Most cases have occurred in the mid-Atlantic and southeastern states in the United States. (For more information on this disorder, choose “Human Monocytic Ehrlichiosis” 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. 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 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 stiffness and pain of the large joints (infectious arthritis), especially the knees. Such symptoms may tend to occur in recurrent cycles. In severe cases, heart muscle (myocardial) and/or neurological 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). 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.)

Toxic Shock Syndrome is a rare infectious disorder caused by the bacterium Staphylococcus aureus, which produces and secretes a poison (toxin [enterotoxin F]). The initial symptoms of Toxic Shock Syndrome may include a sudden high fever, nausea, vomiting, diarrhea, headache, sore throat (pharyngitis), and/or a characteristic skin rash that resembles a bad sunburn. Later symptoms may include confusion, abnormally low blood pressure (hypotension), and/or abnormal liver function. Without early diagnosis and appropriate treatment, life-threatening symptoms may result. Most cases of Toxic Shock Syndrome occur in menstruating females, possibly in association with the prolonged use of high-absorbency tampons. However, some females who have not used tampons and some males have been affected by the disorder. (For more information on this disorder, choose “Toxic Shock” 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 Sennetsu Fever. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

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Standard Therapies

Sennetsu Fever 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 circulating 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; chest X-rays may reveal abnormalities in the lungs (pulmonary infiltrates).

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. Sennetsu Fever may be diagnosed by observing the antibody response in a patient's blood serum to the bacterium Ehrlichia sennetsu.

Measurable, diagnostic rises in antibody response to the Ehrlichia sennetsu bacteria may not occur until several weeks after the onset of Sennetsu Fever. 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.

Information in the medical literature indicates that because it may be difficult to differentiate Human Ehrlichial infection, such as Sennetsu Fever, 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 known vectors for Ehrlichial infection. If Sennetsu Fever 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 Sennetsu Fever usually entails standard doses of tetracycline antibiotics. The antibiotic drugs doxycycline or minocycline have also been administered to treat this disease. In severe cases of Sennetsu Fever, hospitalization may be required. Other treatment is symptomatic and supportive.

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Clinical Trials and Studies

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

Email: [email protected]

For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

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References

TEXTBOOKS

Harrison’s Principles of Internal Medicine, 13th Ed.: Kurt J. Isselbacher, M.D. et al., Editors; McGraw-Hill, Inc., 1994. P. 756.

Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 4th Ed.: Gerald L. Mandell, M.D. et al., Editors; Churchill Livingstone Inc., 1995. Pp. 1747-52, 2143.

Infectious Diseases: Sherwood L. Gorbach, John G. Bartlett, and Neil R. Blacklow, Editors; W.B. Saunders Company, 1992. Pp. 1312-14.

JOURNAL ARTICLES

Ehrlichia Ewingii, A Newly Recognized Agentof Human Ehrlichiosis. R.S. Buller et al.; New Eng J Med (July 15 1999; 341(3)). Pp. 148-55.

Ehrlichiosis: Ticks, Dogs and Doxycycline (editorial). J.L. Goodman; New Eng J Med (July 15 1999; 341(3)).

Direct Cultivation of the Causative Agent of Human Granulocytic Ehrlichiosis. J.L. Goodman et al.; New Eng J Med (Jan 25 1996; 334(4)). Pp. 209-15.

Ehrlichiosis – in Pursuit of an Emerging Infection (editorial). W. Schaffner et al.; New Eng J Med (Jan 25 1996; 334(4)). Pp. 262-63.

Identification of a Granulocytotropic Ehrlichia Species as the Etiologic Agent of Human Disease. S.M. Chen et al.; J Clin Microbiol (Mar 1994; 32(3)). Pp. 589-95.

Emergence of the Ehrlichioses as Human Health Problems. D.H. Walker et al.; Emerging Infectious Diseases (Jan-Mar 1996; 2(1)). Pp. 1-16.

Seroepidemiology of Infections Due to Spotted Fever Group Rickettsiae and Ehrlichia Species in Military Personnel Exposed in Areas of the United States Where Such Infections are Enemic. S.J. Yevich et al.; J Infect Dis (May 1995; 171(5)). Pp. 1266-73.

Serologic Cross-Reactions Among Ehrlichia Equi, Ehrlichia Phagocytophlia and Human Phagocytophila and Human Granulocytic Ehrlichia. J.S. Dumler et al.; J Clin Microbiol (May 1995; 33(5)). Pp. 1098-103.

Ehrlichiosis in a Golf-Oriented Retirement Community. S.M. Standaert et al.; New Eng J Med (Aug 17 1995; 333(7)). Pp. 420-25.

Human Granulocytic Ehrlichiosis in the Upper Midwest United States. A New Species Emerging? J.S. Bakken et al.; JAMA (Jul 20 1994; 272(3)). Pp. 212-18.

Human Ehrlichiosis in Adults After Tick Exposure. Diagnosis Using Polymerase Chain Reaction. E.D. Everett et al.; Ann Intern Med (May 1 1994; 120(9)). Pp. 730-35.

Serologic Evidence for Human Ehrlichiosis in Africa. P. Brouqui et al.; Eur J Epidemiol (Dec 1994; 10(6)). Pp. 695-98.

A Case of Human Ehrlichiosis Acquired in Mali: Clinical and Laboratory Findings. I.J. Uhaa et al.; Am J Trop Med Hyg (Feb 1992; 46(2)). Pp. 161-64.

In Vitro Anticiotic Susceptibility of the Newly Recognized Agent of Ehrlichiosis in Humans, Ehrlichia Chaffeensis. P. Brouqui et al.; Antimicrob Agents Chemother (Dec 1992; 36(12)). Pp. 2799-803.

Detection of the Etiologic Agent of Human Ehrlichiosis by Polymerase Chain Reaction. B.E. Anderson et al.; J Clin Microbiol (Apr 1992; 30(4)). Pp. 775-80.

In Vitro Susceptibility of Ehrlichia Sennetsu to Antibiotics. P. Brouqui et al.; Antimicrob Agents Chemother (Aug 1990; 34(8)). Pp. 1593-96.

FROM THE INTERNET

https://www.cdc.gov/ncidod/dvrd/ehrlichia/Organisms/Organism.htm

https://rarediseases.info.nih.gov/asp/diseases/diseaseinfo.asp?ID=120

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