Anaplasmosis is an infectious disease spread by ticks. It is caused by Anaplasma phagocytophilum, a type of bacteria that can only survive inside the cells of its host and is classified as gram-negative (a laboratory term describing its outer cell structure). People become infected mainly through the bite of blacklegged ticks, Ixodes scapularis in the northeastern and midwestern United States, and Ixodes pacificus on the West Coast.
The disease affects humans as well as many animals, including deer, cattle, sheep, and dogs. These animals can carry the bacteria without always showing illness, helping it remain in the environment.
Since anaplasmosis became a reportable disease in the United States in 2000, the number of diagnosed cases has increased significantly, from about 348 cases in 2000 to more than 5,700 cases in 2017. Between 2008 and 2012, the average rate was roughly 6.3 cases per million people each year.
Symptoms usually appear 5 to 21 days after a bite from an infected tick. They often resemble the flu and may include fever, severe headache, chills, muscle aches, and fatigue. Some people also experience nausea, vomiting, loss of appetite, abdominal pain, or diarrhea. Blood tests may show low levels of white blood cells (leukopenia), low platelets (thrombocytopenia), or higher-than-normal liver enzymes, which can indicate stress on the liver.
The recommended treatment for both adults and children is the antibiotic doxycycline. When treatment begins early, most people start to feel better within one to two days. For those who cannot take doxycycline, such as individuals with certain allergies, other antibiotics like rifampin may be used with medical guidance.
Although many cases are mild, anaplasmosis can become severe, especially in older adults or people with weakened immune systems. From 2008 to 2012, about 31% of reported patients required hospitalization, and approximately 0.3% of cases were fatal. If the disease is not treated promptly, it can lead to serious complications involving multiple organs, including the kidneys, lungs, heart, blood system, or central nervous system.
Because the same ticks can carry other disease-causing organisms, including those responsible for Lyme disease and babesiosis, people can sometimes be infected with more than one pathogen at the same time.
Prevention focuses on avoiding tick bites by using insect repellent, wearing protective clothing, steering clear of tick-infested areas, and carefully checking the body for ticks after spending time in grassy or wooded environments.
Historical Background of Anaplasmosis
Anaplasmosis, in humans, is a relatively recent diagnostic discovery compared with other tick-borne diseases. Although the bacterium Anaplasma phagocytophilum had been recognized for decades as a cause of illness in livestock, particularly cattle, sheep, and goats, the infection was not clearly identified as a human disease until the mid-1990s. Before this time, human cases were likely overlooked or incorrectly attributed to other febrile (fever-causing) tick-borne illnesses because the early symptoms are non-specific and resemble common viral infections.
The first confirmed human cases were documented in the upper Midwestern United States, especially in Wisconsin and Minnesota, regions where blacklegged ticks were already known to transmit other pathogens. As diagnostic testing improved, especially the availability of polymerase chain reaction (PCR) assays capable of detecting bacterial DNA, the condition became easier to recognize. Increased awareness among healthcare providers also contributed to a steady rise in reported cases.
The growing number of diagnosed infections over the past two decades is closely linked to the expanding geographic range of blacklegged ticks. Warmer temperatures, suburban development near wooded habitats, and rising deer populations (the primary host for adult ticks) have all contributed to the spread of these ticks into new regions. As a result, areas that previously reported few or no cases of anaplasmosis now experience consistent seasonal activity, making the disease an important emerging public health concern.
Distinction From Other Tick-Borne Illnesses
Anaplasmosis often resembles other tick-borne diseases, which can complicate diagnosis, especially during the early stages of illness. The condition shares several symptoms, such as fever, headache, and muscle aches, with two commonly encountered infections: Lyme disease and ehrlichiosis. However, these diseases differ in their causative organisms, the types of cells they infect, and the clinical features that may help distinguish them.
Lyme disease, caused by the bacterium Borrelia burgdorferi, primarily affects connective tissue and can involve the skin, joints, heart, and nervous system. Unlike anaplasmosis, Lyme disease frequently presents with a characteristic skin finding, the erythema migrans rash, a circular or “bull’s-eye” pattern that develops at the site of a tick bite. This rash is a key diagnostic clue and is present in most Lyme disease cases, whereas anaplasmosis rarely causes visible skin changes. Because anaplasmosis lacks such a distinctive sign, clinicians rely more heavily on symptom patterns, laboratory findings, and known tick exposure when evaluating patients.
Ehrlichiosis, caused by Ehrlichia species such as Ehrlichia chaffeensis, has symptoms nearly identical to anaplasmosis. However, the two diseases can be distinguished by the types of white blood cells they target. Anaplasmosis infects neutrophils, a major component of the immune system responsible for fighting bacterial infections, whereas ehrlichiosis infects monocytes, another type of immune cell involved in inflammation and immune regulation. Although laboratory confirmation is possible, testing may not always be immediately available, so early clinical judgment is essential.
Because blacklegged ticks can carry multiple pathogens at the same time, co-infection is also possible. A person bitten by a single infected tick may develop anaplasmosis together with Lyme disease, babesiosis, or other tick-borne conditions. These overlapping infections can lead to more severe symptoms, complicate the clinical picture, and influence treatment choices.
Causes of Anaplasmosis
Anaplasmosis results from infection by a specific type of bacterium and spreads primarily through arthropod vectors.
Anaplasma phagocytophilum Bacteria
Anaplasma phagocytophilum is the pathogen responsible for human granulocytic anaplasmosis. It is classified as an obligate intracellular bacterium, meaning it cannot live or reproduce outside a host cell. It belongs to the family Anaplasmataceae, a group of bacteria known for infecting blood cells and being transmitted through arthropod vectors such as ticks.
A defining feature of A. phagocytophilum is its ability to invade and survive inside neutrophils, which are white blood cells responsible for early defense against bacterial infections. Once inside a neutrophil, the bacterium resides in a membrane-bound vacuole, forming clusters called morulae, which can sometimes be seen under a microscope during diagnostic testing. By living inside immune cells, the bacterium avoids detection, modifies host cell signaling, and interferes with normal immune responses. These disruptions contribute to the symptoms of anaplasmosis, such as fever, fatigue, and immune dysregulation.
The bacterium replicates within the infected cell until the cell bursts or otherwise becomes dysfunctional, allowing the bacteria to move on and infect additional cells. This cycle of intracellular growth is one reason early treatment with antibiotics, especially doxycycline, is crucial, as it interrupts bacterial replication before widespread infection occurs.
Although A. phagocytophilum infects humans, it also infects a wide range of mammals, including deer, small rodents, dogs, sheep, and cattle. These animals act as reservoir hosts, meaning they harbor the bacterium without necessarily showing severe illness and help maintain the pathogen within ecosystems where tick vectors are present.
Transmission Pathways
Anaplasmosis is transmitted primarily through the bite of infected ticks. The main vectors are Ixodes species, commonly known as blacklegged ticks or deer ticks. In the United States, the most important vectors are:
- Ixodes scapularis – found in the northeastern, mid-Atlantic, and north-central regions
- Ixodes pacificus – found along the western coast
Ticks acquire A. phagocytophilum by feeding on infected wildlife. White-footed mice, chipmunks, shrews, and deer play key roles in sustaining the bacterium in nature. Nymphal ticks (immature ticks) are particularly important in transmission to humans because they are very small, about the size of a poppy seed, and often go unnoticed.
For transmission to occur, an infected tick typically must remain attached to the skin for 24 to 48 hours. During this time, the bacterium moves from the tick’s gut to its salivary glands and enters the human bloodstream. Because the initial tick bite is painless and easy to overlook, many infected individuals do not recall being bitten.
Although tick bites account for the vast majority of human cases, several less common transmission pathways have been reported:
- Blood transfusions: Because the bacterium infects blood cells, transfusion-related transmission is possible. Screening measures reduce but do not completely eliminate this risk.
- Organ transplantation: Extremely rare but biologically plausible, given the presence of infected white blood cells in donor organs.
- Congenital transmission: Rare cases of transmission from mother to fetus have been reported, although they are uncommon compared to tick-borne transmission.
- Exposure in laboratory settings: Accidental infection may occur among laboratory personnel handling infected blood or ticks, though such cases are rare.
Symptoms and Clinical Presentation
Anaplasmosis typically begins with flu-like symptoms and can escalate to more serious health issues if untreated.
Early Signs
Symptoms typically appear 5 to 14 days after the bite of an infected tick. The onset is often sudden, with many patients reporting that they felt well earlier in the day and rapidly developed symptoms by evening. The most common early signs include:
- Fever, often high and persistent
- Chills or rigors (shaking chills)
- Severe fatigue or weakness
- Headache, often generalized and intense
- Muscle aches (myalgia)
- General malaise, described as “feeling unwell”
Gastrointestinal symptoms occur in a minority of cases and may include nausea, vomiting, diarrhea, or abdominal discomfort. Unlike Lyme disease, a rash is uncommon, reported in less than 10% of cases, and usually appears only in individuals with co-infections such as Lyme disease or babesiosis.
Laboratory findings provide important diagnostic clues. Patients frequently show:
- Leukopenia — low white blood cell count
- Thrombocytopenia — low platelet count
- Elevated liver enzymes — indicating mild liver inflammation
These lab abnormalities may appear early in the illness, even before symptoms fully develop, and help distinguish anaplasmosis from viral infections or conditions with similar presentations.
Severe Complications
If not treated promptly, anaplasmosis can progress to severe disease, especially in older adults, individuals with suppressed immune systems, or people with delayed treatment. Serious complications may begin several days after symptom onset and can affect multiple organ systems.
Potential complications include:
- Respiratory failure — difficulty breathing requiring oxygen support or mechanical ventilation
- Kidney failure, sometimes requiring temporary dialysis
- Bleeding disorders due to very low platelet levels
- Sepsis-like syndrome and severe systemic inflammation
- Neurological symptoms, such as confusion, difficulty concentrating, or, in advanced cases, altered mental status
- Secondary infections, resulting from compromised immune function
Hospitalization rates for anaplasmosis vary by study but generally fall between 25% and 40%, with severe outcomes more common in patients who are untreated for several days after symptom onset. The fatality rate is low, around 0.3%, but increases significantly in high-risk individuals, including those who delay care.
Symptoms in Children and Elderly
Children frequently exhibit less severe symptoms but may experience high fever and irritability. Older adults, particularly those over 60, often endure more intense manifestations including pronounced weakness and confusion.
The elderly are more susceptible to severe disease progression, partly due to weakened immune function. Monitoring in this group requires heightened clinical attention to prevent rapid deterioration.
Risk Factors
Anaplasmosis risk depends largely on environmental exposure and the individual’s immune status. Certain behaviors and underlying health conditions increase the likelihood of contracting the disease.
Tick Exposure
The primary risk factor for anaplasmosis is contact with infected Ixodes ticks, which transmit the Anaplasma phagocytophilum bacterium. People who spend time in wooded or grassy areas, especially in the northeastern and upper midwestern United States, are more susceptible.
Risk is highest during spring and summer when ticks are most active. Protective measures such as wearing long clothing, using insect repellents containing DEET, and performing thorough tick checks after outdoor activities reduce exposure.
Residential proximity to tick habitats and outdoor occupations, like forestry or landscaping, also elevate risk. Not all ticks carry the bacteria, but even a small chance leads to increased overall risk for frequent outdoor contact.
Immunocompromised Populations
Individuals with weakened immune systems face increased severity and complications from anaplasmosis. This group includes the elderly, patients undergoing chemotherapy, organ transplant recipients, and those with HIV/AIDS.
Immunocompromised persons may experience prolonged illness, higher rates of hospitalization, and more intensive treatment requirements compared to healthy individuals. Early diagnosis and prompt antibiotic therapy are especially critical for this group.
Additionally, chronic conditions such as diabetes or liver disease may compromise immune response, indirectly raising susceptibility to severe infection. Healthcare providers should maintain heightened vigilance in these patients during tick season.
Diagnosis of Anaplasmosis
Clinicians begin by assessing whether the patient may have been exposed to ticks. This includes asking about recent time spent in areas where ticks are common, such as forests or grassy fields, and whether the patient recalls a tick bite within the previous one to two weeks. Many people do not notice being bitten, so simply visiting these environments is enough to raise suspicion. Because early symptoms of anaplasmosis resemble the flu or other common infections, laboratory testing is essential for diagnosis.
Polymerase chain reaction (PCR) testing of whole blood is the most accurate method for confirming anaplasmosis in its early stages. PCR detects the DNA of Anaplasma phagocytophilum, the bacterium that causes the disease. It works best in the first week of illness, when the number of bacteria in the bloodstream is highest. A positive PCR result strongly supports the diagnosis. However, a negative result does not fully exclude the disease, especially if antibiotics have already been started, because treatment quickly lowers bacterial levels. For this reason, PCR is most reliable when performed before antibiotics are given.
Microscopic examination of a stained blood smear can also provide clues. In this test, laboratory staff look for morulae, small clusters of bacteria, inside neutrophils, a type of white blood cell. Finding morulae supports the diagnosis, but this method is less sensitive because the clusters are not present in all patients and are difficult to detect. The accuracy of this approach depends on both the timing of the illness and the expertise of the person examining the slide.
Serologic testing, which looks for antibodies produced by the immune system, is another important diagnostic tool. The most common method is the indirect immunofluorescence assay (IFA). Antibodies often do not appear until later in the illness, so blood tests taken in the first week may be negative. A confirmed diagnosis requires a fourfold increase in IgG antibody levels between an early blood sample and another collected two to four weeks later. Because of this delay, serology is less helpful for immediate treatment decisions but is useful for confirming past infection and for public health surveillance. IgM antibodies appear earlier but are less reliable due to a higher chance of false-positive results.
Routine blood tests often show abnormalities that support, but do not prove, the diagnosis. These may include low white blood cell counts, low platelet counts, and elevated liver enzyme levels. These findings reflect the way the bacteria affect immune cells and the body’s inflammatory response to infection. While these abnormalities can occur in many other illnesses, their presence in a patient with fever and possible tick exposure increases the likelihood of anaplasmosis.
Because anaplasmosis resembles other tick-borne diseases, clinicians must distinguish it from conditions with similar symptoms. These include Lyme disease, ehrlichiosis, and babesiosis, which often occur in the same regions and seasons. Lyme disease usually presents with a distinctive rash, which is uncommon in anaplasmosis. Ehrlichiosis appears very similar but affects a different type of white blood cell. Babesiosis causes fever and anemia and can be identified by parasites visible inside red blood cells on a blood smear. Certain viral infections, such as influenza, COVID-19, and early hepatitis, can also resemble anaplasmosis, particularly when respiratory or digestive symptoms are present.
Other medical conditions, including sepsis, autoimmune diseases, blood disorders, and some cancers, can also cause fever, low platelet counts, and elevated liver enzymes, so they must be considered as well. A thorough patient history is therefore essential. Information about outdoor activities, travel to areas where ticks are common, interactions with animals, and recent seasonal patterns helps narrow down the diagnosis. In regions where blacklegged ticks (the main carriers of the bacterium) are common, clinicians tend to consider anaplasmosis earlier in the diagnostic process, especially from late spring through early fall.
Accurate diagnosis depends on combining clinical evaluation with appropriate laboratory tests. Because no single test is reliable at all stages of the disease, physicians often use a combination of PCR testing, blood smear examination, and antibody testing to reach a final diagnosis.
Treatment Protocols
Treatment of anaplasmosis involves targeted medication and interventions to relieve symptoms and prevent complications.
Antibiotic Therapy
The recommended first-line treatment for both adults and children is doxycycline. For adults, the standard dose is 100 mg taken twice daily, typically for 10 to 14 days. This duration is chosen not only to eliminate Anaplasma phagocytophilum but also to provide coverage for potential co-infections, such as Lyme disease, which are common in areas where Ixodes ticks are prevalent. Clinical improvement often begins within 24 to 48 hours of starting doxycycline, and persistent fever beyond this period may suggest either a delayed response, an underlying co-infection, or an incorrect diagnosis. Because doxycycline is highly effective, continued symptoms despite treatment warrant further evaluation.
Although doxycycline is safe for most patients, alternative antibiotics may be needed in specific circumstances. Rifampin is the most commonly used substitute for individuals with severe doxycycline allergies or certain contraindications, such as pregnancy. Studies indicate that rifampin is effective at reducing bacterial levels, but its use is limited because it does not treat common co-infections like Lyme disease or babesiosis. Consequently, patients treated with rifampin require closer monitoring for incomplete clinical response.
Other antibiotics, including β-lactams or macrolides, are not effective against Anaplasma species, so they should not be used. Regardless of the antibiotic chosen, clinicians generally continue therapy for at least three days after the fever resolves and until the patient shows clear signs of clinical improvement.
Supportive Care
Fever, headache, and muscle aches are typically managed with antipyretic medications such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). Maintaining adequate hydration is critical, particularly for individuals experiencing nausea, vomiting, or limited oral intake. In more serious cases, especially those involving respiratory difficulties, organ dysfunction, or dangerously low platelet counts, hospitalization may be required. Hospital-based care allows for intravenous fluids, close monitoring of vital signs, and timely intervention if complications arise.
Routine blood tests track platelet and white blood cell counts, liver enzyme levels, and kidney function. Because anaplasmosis often causes leukopenia and thrombocytopenia, these values help clinicians assess whether the patient is improving or developing complications.
Patients with severe anemia, bleeding problems, or profound thrombocytopenia may require transfusions, although this is uncommon. In cases of co-infection, particularly with babesiosis, which infects red blood cells, additional treatments such as atovaquone and azithromycin may be necessary. Identifying co-infections early ensures that all contributing pathogens are addressed and reduces the risk of treatment failure.
Preventive Measures
Preventing anaplasmosis relies heavily on reducing exposure to ticks, especially in regions where Ixodes ticks are common. Personal protective measures are the first line of defense when spending time in forests, brush, tall grasses, or leaf-littered environments. Wearing long sleeves, long pants, and closed footwear creates a physical barrier that makes it more difficult for ticks to reach the skin. Light-colored clothing is often recommended because it makes it easier to spot ticks before they attach. Tucking pants into socks and shirts into pants further limits access points for ticks seeking to move upward toward areas of thinner skin. Clothing treated with permethrin, a synthetic insecticide that repels and kills ticks on contact, has been shown in multiple studies to reduce tick bites significantly. Commercially pre-treated clothing is available, and individuals can also apply permethrin spray themselves following product instructions.
Using Environmental Protection Agency (EPA)-approved insect repellents on exposed skin adds an additional layer of chemical protection. Products containing DEET, picaridin, IR3535, or oil of lemon eucalyptus provide varying durations of repellent activity and can substantially lower the likelihood of tick attachment. DEET and picaridin are among the most effective and widely studied, and they can be safely used when applied according to label directions. Repellents should be applied before entering tick-prone areas and re-applied as needed, particularly during warmer months when ticks are most active. For children, caregivers should apply repellents carefully, avoiding the hands, eyes, and mouth. Combining skin repellent with permethrin-treated clothing offers the highest level of individual protection.
Post-exposure preventive behaviors are equally important. After returning indoors, individuals should perform a careful, full-body tick check, paying special attention to areas where ticks commonly attach, such as the scalp, behind the ears, under the arms, around the waist, and behind the knees. Showering within two hours of outdoor exposure has been shown to reduce the risk of tick-borne illnesses, likely because it helps wash away unattached ticks. Pets should also be inspected, as dogs and cats can inadvertently carry ticks into homes. Using veterinarian-recommended tick preventives such as oral medications, topical treatments, or tick collars, reduces the risk of pets becoming hosts and transporting ticks to humans.
Environmental modification plays a major role in reducing tick presence around homes and recreational areas. Ticks thrive in shady, humid habitats such as leaf litter, underbrush, woodpiles, and overgrown vegetation. Regular landscaping practices, such as mowing lawns, removing leaf litter, trimming shrubs, and keeping play areas away from wooded edges, can significantly reduce tick density. Creating a physical barrier of wood chips or gravel between lawns and adjacent forested areas discourages ticks from migrating into frequently used outdoor spaces. Fencing may help limit access of deer, which serve as important reproductive hosts for adult ticks.
Most Anaplasma phagocytophilum transmission requires the tick to remain attached for at least 24 to 48 hours. Therefore, removing ticks early can effectively prevent illness. Fine-tipped tweezers should be used to grasp the tick as close to the skin as possible, pulling upward with steady, even pressure. Twisting or crushing the tick should be avoided, as this can increase the risk of pathogen exposure. After removal, the bite site should be cleaned with soap and water or antiseptic. Individuals may choose to save the tick in a sealed container for identification, although routine tick testing is not recommended for clinical decision-making.
Long-Term Health Impacts
Anaplasmosis can lead to varying outcomes after the initial infection. Some patients recover fully, while others may experience ongoing complications. The recovery process and potential chronic effects depend on timely treatment and individual health factors.
Recovery and Prognosis
Most patients treated with appropriate antibiotics recover within days to weeks. Early intervention greatly reduces the risk of severe complications. Symptoms such as fever, fatigue, and muscle aches typically subside after a 10-14 day antibiotic course.
Delayed or inadequate treatment can prolong illness and increase hospitalization risks. Those with weakened immune systems or underlying conditions may experience slower recovery or more severe symptoms. Follow-up care is important to monitor for any residual effects and ensure full recovery.
Potential Chronic Effects
Chronic health issues related to anaplasmosis are uncommon but possible. Some patients report lingering fatigue and joint pain lasting months after treatment. These symptoms do not always indicate active infection but can affect quality of life.
Rarely, untreated anaplasmosis may cause complications such as respiratory failure, bleeding disorders, or neurological problems. Long-term immune system changes have not been fully documented. Continuous medical evaluation is necessary in cases with persistent or unusual symptoms.
Anaplasmosis in Animals
Anaplasmosis affects various animal species with significant differences in clinical signs and management. Each group requires specific attention based on their environment, use, and susceptibility to the disease.
Livestock
In livestock, anaplasmosis primarily affects cattle, sheep, and goats. Cattle are the most commonly impacted, showing symptoms such as fever, anemia, weight loss, and reduced milk production. The disease is transmitted by ticks, biting flies, and sometimes contaminated equipment.
Key clinical signs in livestock include:
- Pale mucous membranes
- Jaundice
- Labored breathing
Diagnosis often involves blood tests to detect Anaplasma organisms or antibodies. Treatment consists mainly of antibiotics like oxytetracycline. Preventive measures focus on tick control, vaccination, and vector management.
Economic losses arise from decreased productivity and increased veterinary costs, making early detection and intervention critical.
Companion Animals
In companion animals, especially dogs, anaplasmosis is caused chiefly by Anaplasma phagocytophilum and Anaplasma platys. Clinical signs include fever, lethargy, joint pain, and thrombocytopenia (low platelet counts). These symptoms can mimic other tick-borne illnesses, complicating diagnosis.
Routine blood tests and serology confirm infection. Treatment involves doxycycline, usually with a course lasting 2 to 4 weeks. Tick prevention methods such as collars, topical agents, or environmental control are essential to reduce transmission.
Infected pets can recover fully with treatment but may require ongoing monitoring for relapse or complications.