Human granulocytic anaplasmosis

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Human granulocytic anaplasmosis
SynonymsHuman granulocytic ehrlichiosis (HGE) [1] [2]
Anaplasma phagocytophilum cultured in human promyelocytic cell line HL-60.jpg
Anaplasma phagocytophilum cultured in human
Specialty Infectious disease   Blue pencil.svg

Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum , an obligate intracellular bacterium that is typically transmitted to humans by ticks of the Ixodes ricinus species complex, including Ixodes scapularis and Ixodes pacificus in North America. These ticks also transmit Lyme disease and other tick-borne diseases. [3]

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. Tick-borne illnesses are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. Because individual ticks can harbor more than one disease-causing agent, patients can be infected with more than one pathogen at the same time, compounding the difficulty in diagnosis and treatment. As of 2016, 16 tick-borne diseases of humans are known.

<i>Anaplasma phagocytophilum</i> species of bacterium

Anaplasma phagocytophilum is a Gram-negative bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.

<i>Ixodes ricinus</i> species of hard-bodied tick

Ixodes ricinus, the castor bean tick, is a chiefly European species of hard-bodied tick. It may reach a length of 11 mm (0.43 in) when engorged with a blood meal, and can transmit both bacterial and viral pathogens such as the causative agents of Lyme disease and tick-borne encephalitis.


The bacteria infect white blood cells called neutrophils, causing changes in gene expression that prolong the life of these otherwise short-lived cells. [4]

Signs and symptoms

Signs and symptoms may include:

Fever common medical sign characterized by elevated body temperature

Fever, also known as pyrexia and febrile response, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C. The increase in set point triggers increased muscle contractions and causes a feeling of cold. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure. This is more common in young children. Fevers do not typically go higher than 41 to 42 °C.

Headache pain in the head or neck

Headache is the symptom of pain anywhere in the region of the head or neck. It occurs in migraines, tension-type headaches, and cluster headaches. Frequent headaches can affect relationships and employment. There is also an increased risk of depression in those with severe headaches.

Myalgia, or muscle pain, is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections. Longer-term myalgias may be indicative of a metabolic myopathy, some nutritional deficiencies or chronic fatigue syndrome.

Symptoms may be minor, as evidenced by surveillance studies in high-risk areas. Gastrointestinal tract symptoms occur in less than half of patients and a skin rash is seen in less than 10% of patients. [5] It is also characterized by a low number of platelets, a low number of white blood cells, and elevated serum transaminase levels in the majority of infected patients. [5] Even though people of any age can get HGA, it is usually more severe in the aging or immune-compromised. Some severe complications may include respiratory failure, kidney failure, and secondary infections.

Gastrointestinal tract organ system within humans and other animals pertaining the stomach and intestines

The gastrointestinal tract is an organ system within humans and other animals which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. The mouth, esophagus, stomach and intestines are part of the gastrointestinal tract. Gastrointestinal is an adjective meaning of or pertaining to the stomach and intestines. A tract is a collection of related anatomic structures or a series of connected body organs.

Thrombocytopenia A blood platelet disease characterized by a low platelet count in the blood.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood.

Leukopenia is a decrease in the number of white blood cells (leukocytes) found in the blood, which places individuals at increased risk of infection.


A. phagocytophilum is transmitted to humans by Ixodes ticks. These ticks are found in the US, Europe, and Asia. In the US, I. scapularis is the tick vector in the East and Midwest states, and I. pacificus in the Pacific Northwest. [6] In Europe, the I. ricinus is the main tick vector, and I. persulcatus is the currently known tick vector in Asia. [7]

The major mammalian reservoir for A. phagocytophilum in the eastern United States is the white-footed mouse, Peromyscus leucopus. Although white-tailed deer and other small mammals harbor A. phagocytophilum, evidence suggests that they are not a reservoir for the strains that cause HGA. [8] [9] A tick that has a blood meal from an infected reservoir becomes infected themselves. If an infected tick then latches onto a human the disease is then transmitted to the human host and A.phagocytophilum symptoms can arise. [10]

Anaplasma phagocytophilum shares its tick vector with other human pathogens, and about 10% of patients with HGA show serologic evidence of coinfection with Lyme disease, babesiosis, or tick-borne meningoencephalitis. [11]

While it is rare, it is possible for HGA to be transmitted human-to-human via a blood transfusion, in which case it is called Transfusion-Transmitted Anaplasmosis (TTA). [12]

Major surface proteins

Lots of MSPs are found in Anaplasma and the ones that interact with Anaplasma can mainly be found in A. marginale and A. phagocytophilum. [13] There are many different phenotypic traits that are associated with MSPs, because each MSP can only infect certain animals in certain conditions. [13] A. phagocytophilum infects the most vast array of living things, including humans, and all around the world. [13] A. marginale evolved to be more specific in infecting animals, such as deer and cattle in the subtropics and tropics. [13] The main difference between these two MSPs is that the host cell for A. phagocytophilum is the granulocyte, while the host cell for A. marginale is erythrocytes. [13] It is likely that these MSPs coevolved, because they had previously interacted via tick-pathogen interaction. [13]

Anaplasma MSPs can not only cooperate with vertebrates, but also invertebrates, which make these phenotypes evolve faster than others, because they have a lot of selective forces acting on them. [13]


Clinically, HGA is essentially indistinguishable from human monocytic ehrlichiosis, the infection caused by Ehrlichia chaffeensis , and other tick-borne illnesses such as Lyme disease may be suspected. [14] As Ehrlichia serologies can be negative in the acute period, PCR is very useful for diagnosis. [15]


Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment. [7] The best way to prevent HGA is to prevent getting tick bites. [16]


Doxycycline is the treatment of choice. If anaplasmosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been shown to improve outcomes. [14] Presentation during early pregnancy can complicate treatment. Doxycycline compromises dental enamel during development. [17] Although rifampin is indicated for post-delivery pediatric and some doxycycline-allergic patients, it is teratogenic. Rifampin is contraindicated during conception and pregnancy. [18]

If the disease is not treated quickly, sometimes before the diagnosis, the person has a high chance of mortality. [7] Most people make a complete recovery, though some people are intensively cared for after treatment. [7] A reason for a person needing intensive care is if the person goes too long without seeing a doctor or being diagnosed. [7] The majority of people, though, make a complete recovery with no residual damage. [7]


The first outbreak of Human Granulocytic Anaplasmosis (HGA) in the United States was in a patient in early 1990 in Wisconsin. He was kept in the hospital in Minnesota for testing, but died without a diagnosis. [7] Over the next couple of years, many people within the same area of Wisconsin and Minnesota had come down with the same symptoms. [7] It was discovered in 1994 that it was Human Granulocytic Ehrlichiosis (HGE), later to be known as HGA. [10]


From the first reported case in 1994 until 2010, HGA's rates of incidence have exponentially increased. [19] This is likely because HGA is found where there are ticks that carry and transmit Lyme disease, also known as Borrelia burgdorferi, and babesiosis, which is found in the northeastern and midwestern parts of the United States, which has seemingly increased in the past couple of decades. [19] Before 2000, there were less than 300 cases reported per year. In 2000, there were only 350 reported cases. [19] From 2009-2010, HGA experienced a 52% increase in the number of cases reported. [19]


Although the infectious agent is known to be from the Anaplasma genus, the term "human granulocytic ehrlichiosis" (HGE) is often used, reflecting the prior classification of the organism. E. phagocytophilum and E. equi were reclassified as Anaplasma phagocytophilum.

See also

Related Research Articles

Lyme disease infectious disease caused by Borrelia bacteria, spread by ticks

Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by a bacterium named Borrelia spread by ticks. The most common sign of infection is an expanding area of redness on the skin, known as erythema migrans, that appears at the site of the tick bite about a week after it occurred. The rash is typically neither itchy nor painful. Approximately 70–80% of infected people develop a rash. Other early symptoms may include fever, headache and tiredness. If untreated, symptoms may include loss of the ability to move one or both sides of the face, joint pains, severe headaches with neck stiffness, or heart palpitations, among others. Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, people develop shooting pains or tingling in their arms and legs. Despite appropriate treatment, about 10 to 20% of people develop joint pains, memory problems, and tiredness for at least six months.

Babesiosis malaria-like parasitic disease caused by infection with Babesia, a genus of Apicomplexa

Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a type of Apicomplexa. Human babesiosis transmission via tick bite is most common in the Northeastern and Midwestern United States and parts of Europe, and sporadic throughout the rest of the world. It occurs in warm weather. People can get infected with Babesia parasites by the bite of an infected tick, by getting a blood transfusion from an infected donor of blood products, or by congenital transmission. Ticks transmit the human strain of babesiosis, so it often presents with other tick-borne illnesses such as Lyme disease. After trypanosomes, Babesia is thought to be the second-most common blood parasite of mammals, and they can have a major impact on health of domestic animals in areas without severe winters. In cattle the disease is known as Texas cattle fever, redwater, or piroplasmosis.

Erythema migrans

Erythema migrans refers to a rash often seen in the early stage of Lyme disease, and can also be caused by southern tick-associated rash illness (STARI). It can appear anywhere from one day to one month after a tick bite. This rash does not represent an allergic reaction to the bite, but rather an actual skin infection of one of the Lyme bacteria species from the genus Borrelia.

<i>Dermacentor variabilis</i> species of arachnid

Dermacentor variabilis, also known as the American dog tick or wood tick, is a species of tick that is known to carry bacteria responsible for several diseases in humans, including Rocky Mountain spotted fever and tularemia. It is one of the most well-known hard ticks. Diseases are spread when it sucks blood from the host, which could take several days for the host to experience some symptoms.

A canine vector-borne disease (CVBD) is one of "a group of globally distributed and rapidly spreading illnesses that are caused by a range of pathogens transmitted by arthropods including ticks, fleas, mosquitoes and phlebotomine sandflies." CVBDs are important in the fields of veterinary medicine, animal welfare, and public health. Some CVBDs are of zoonotic concern.

Anaplasmosis disease, mostly animal, caused by bacteria of the genus Anaplasma

Anaplasmosis is a disease caused by a rickettsial parasite of ruminants, Anaplasma spp and is therefore related to rickettsial disease. The microorganisms are Gram-negative, and infect red blood cells. They are transmitted by natural means through a number of haematophagous species of ticks. The Ixodes tick that commonly transmits Lyme disease also spreads anaplasmosis.

Ehrlichiosis is a tickborne bacterial infection, caused by bacteria of the family Anaplasmataceae, genera Ehrlichia and Anaplasma. These obligate intracellular bacteria infect and kill white blood cells.

Ehrlichia is a genus of rickettsiales bacteria that is transmitted to vertebrates by ticks. These bacteria cause the Ehrlichiosis infection, which is considered zoonotic, because the main reservoirs for the disease are animals.

<i>Ixodes scapularis</i> parasit ixodes scapularis

Ixodes scapularis is commonly known as the deer tick or black-legged tick, and in some parts of the US as the bear tick. It is a hard-bodied tick of the eastern and northern Midwestern United States and southeastern Canada. It is a vector for several diseases of animals, including humans and is known as the deer tick owing to its habit of parasitizing the white-tailed deer. It is also known to parasitize mice, lizards, migratory birds, etc. especially while the tick is in the larval or nymphal stage.

Neuroborreliosis, is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus Borrelia. Symptoms of the disease include erythema migrans and flu-like symptoms.

Ehrlichia chaffeensis is an obligate intracellular gram-negative species of rickettsiales bacteria. It is a zoonotic pathogen transmitted to humans by the lone star tick. It is the causative agent of human monocytic ehrlichiosis.

Ehrlichia ewingii is a species of rickettsiales bacteria. It has recently been associated with human infection, and can be detected via PCR serological testing. The name Ehrlichia ewingii was proposed in 1992.

Human monocytotropic ehrlichiosis human disease

Human monocytotropic ehrlichiosis (HME) is a form of ehrlichiosis associated with Ehrlichia chaffeensis. This bacterium is an obligate intracellular pathogen affecting monocytes and macrophages.

Ehrlichiosis ewingii infection is an infectious disease caused by an intracellular bacteria, Ehrlichia ewingii. The infection is transmitted to humans by the tick, Amblyomma americanum. This tick can also transmit Ehrlichia chaffeensis, the bacteria that causes human monocytic ehrlichiosis (HME).

The International Lyme and Associated Diseases Society is a non-profit pressure group which advocates for greater acceptance of the controversial and unrecognized diagnosis "chronic Lyme disease". ILADS was formed by advocates for the recognition of "chronic lyme disease" including physicians, patients and laboratory personnel, and has published alternative treatment guidelines and diagnostic criteria due to the disagreement with mainstream consensus medical views on Lyme disease.

<i>Ixodes persulcatus</i> species of arachnid

Ixodes persulcatus, the taiga tick, is a species of hard-bodied tick distributed from Europe through central and northern Asia to the People’s Republic of China and Japan. The sexual dimorphism of the species is marked, the male being much smaller than the female. Hosts include wild and domestic ungulates, man, dog, rabbit, and other small mammals including the dormouse, Amur hedgehog, and occasionally birds.

The Heartland virus (HRTV) is a tick-borne phlebovirus of the Bhanja virus serocomplex discovered in 2009. The Lone Star Tick transmits the virus to people when feeding on blood. As of 2017, only five Midwestern United States have reported 20 human infections, namely Arkansas, Indiana, Missouri, Oklahoma, and Tennessee; symptoms resemble those of two other tick-borne infections ehrlichiosis and anaplasmosis. The reservoir host is unknown, but deer, raccoon, coyotes, and moose in 13 different states have antibody titers against the virus.


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