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Tick-Borne Threat of Anaplasmosis

Dive into the complexities of anaplasmosis, a tickborne illness caused by Anaplasma phagocytophilum.


Explore its symptoms, diagnostic methods, and treatment options. Learn how to recognize early signs, navigate laboratory findings, and understand the importance of prompt medical attention in combating this emerging health concern.



ANAPLASMOSIS (Part 3)


USA Map of anaplasmosis, tick, Anaplasma
[3]

Anaplasmosis, also known as human granulocytic anaplasmosis, is a tickborne disease caused by the bacterium Anaplasma phagocytophilum.


Blacklegged ticks, Ixodes scapularis, in the eastern United States, and western blacklegged ticks, Ixodes pacificus, on the West Coast are the main causes of infection. Coinfections with other tickborne illness such as Lyme disease have been reported. Infections have occasionally been reported through blood transfusion and organ donation.[32]


Peak transmission is during June to November. Two peaks of increased case reporting usually occur, with the first peak during June–July and a smaller peak during October-November. There are about 4,000 to 5,700 cases reported per year to the CDC.[33]


Signs and Symptoms of Early Illness of Anaplasmosis [34]

Signs and symptoms typically begin within 5-14 days after the bite of an infected tick, and are non-specific. They may include:

  • Fever, chills, rigors

  • Severe headache

  • Malaise

  • Myalgia

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia) in about 20% of cases

  • A non-specific rash occurs in less than 10% of patients with anaplasmosis. As rash is a rare finding in anaplasmosis, if a rash is present, consider a coinfection with Lyme disease, or another tickborne disease.

  • Rarely: Nervous system involvement (e.g., meningoencephalitis, focal paralysis)


Late Illness Symptoms of Anaplasmosis [34]

If treatment is delayed severe illness can occur but is rare. Symptoms may include:

  • Renal or respiratory failure

  • Peripheral neuropathies

  • Disseminated intravascular coagulation (DIC)-like coagulopathies

  • Rhabdomyolysis

  • Hemorrhage


The clinical course of anaplasmosis varies from person to person, and may depend on patient age, co-morbid conditions, immune status and time of treatment.


Laboratory Findings in Anaplasmosis [34]

Laboratory findings can include mild anemia, thrombocytopenia, leukopenia and mild to moderate elevations in hepatic transaminases. However, normal laboratory findings do not rule out possible infection.


Testing for Anaplasmosis [35]

Laboratory testing for anaplasmosis is similar to ehrlichiosis.


Indirect immunofluorescence antibody (IFA) assay for IgG using Anaplasma phagocytophilum antigen, is the standard diagnostic test for anaplasmosis. IgG IFA assays should be performed on paired acute and convalescent serum samples collected 2–4 weeks apart to demonstrate evidence of a fourfold rise. Antibody titers are frequently negative in the first week of illness. Anaplasmosis cannot be confirmed using a single acute antibody test. Between 5–10% of healthy people in some areas might have elevated antibody titers due to past exposure to A. phagocytophilum or similar organisms, which is why comparison of paired, serologic assays provides the best evidence of recent infection. Some reference laboratories offer IgM IFA assays which are not necessarily indicators of acute infection, and might be less specific than IgG antibodies. Therefore, IgM antibody titers alone should not be used for laboratory diagnosis.


Polymerase chain reaction (PCR) amplification can be performed on DNA extracted from whole blood specimens. PCR is most sensitive in the first week of illness, and decreases in sensitivity following the administration of appropriate antibiotics. Unfortunately, a negative result does not rule out the diagnosis. PCR can also be used to amplify DNA in solid tissue and bone marrow specimens for testing.


During the first week of illness a peripheral blood smear might reveal morulae (microcolonies of anaplasmae) in the cytoplasm of granulocytes and is highly suggestive of a diagnosis. However, blood smear examination is relatively insensitive, and should not be relied upon solely to diagnose anaplasmosis. The observance of morulae in a particular cell type cannot reliably differentiate between Anaplasma and Ehrlichia species. If a bone marrow biopsy is performed as part of the investigation of cytopenias, immunostaining of the bone marrow biopsy specimen looking for morulae can diagnose anaplasmosis. They may also be seen in organ biopsies taken for other purposes.


Anaplasma phagocytophilum morela in granulocyte on blood smear
Anaplasma phagocytophilum morela in granulocyte on blood smear [15]

Immunohistochemical stain demonstrating A. phagocytophilum morulae (red) in the spleen
Immunohistochemical stain demonstrating A. phagocytophilum morulae (red) in the spleen [35]

Culture of A. phagocytophilum is only available at specialized laboratories, and routine hospital blood cultures cannot detect the organism


Treatment of Anaplasmosis [36]

Post-tick bite antibiotic prophylaxis is not currently recommended to prevent anaplasmosis.


Doxycycline is recommended as the first-line treatment for anaplasmosis in adults and children of all ages. The dosage in adults is 100 mg every 12 hours, in children under 45 kg (100 lbs.)the dose is 2.2 mg/kg body weight given twice a day.


Patients with suspected anaplasmosis should be treated with doxycycline for 10–14 days to provide appropriate length of therapy for possible concurrent Lyme disease infection. Lack of a clinical response to doxycycline suggests that the patient’s condition might not be due to anaplasmosis, or might be a due to a coinfection. Resistance to doxycycline or relapses in anaplasmosis symptoms after the completion of the recommended course have not been documented.


In cases of life-threatening allergies to doxycycline, severe doxycycline intolerance, and in some pregnant patients for whom the clinical course of anaplasmosis appears mild, rifampin might be considered. Rifampin has been used successfully in several pregnant women with anaplasmosis, and small numbers of children <8 years for a 7–10-day course. However, rifampin is not effective in treating Rocky mountain spotted fever, a disease that might be confused with anaplasmosis, nor is it an effective treatment for a potential Lyme disease coinfection. An infectious disease consult is recommended when treating the pregnant patient.



 

More TICK-BORNE Disease articles: Lyme | Ehrlichiosis | Babesia

The CME version of this article is available for the medical community with an online CME test in the APP.


 

REFERENCES

[3] Tickborne Diseases of the United States, CDC, last reviewed September 22, 2020. Retrieved from: https://www.cdc.gov/ticks/tickbornediseases/overview.html


[15] Tickborne Diseases of the United States, CDC, 5th edition 2018. Retrieved from: https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf


[15A] Signs and Symptoms of Untreated Lyme Disease, CDC, last reviewed: January 15, 2021. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/index.html


[16] Photo credits: Alison Young, Taryn Holman, Yevgeniy Balagula/Dermatlas.org, Lyme Disease Rashes and Look-alikes, CDC, last reviewed: October 9, 2020. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/rashes.html


[17] Photo Credit: Bernard Cohen/Dermatlas.org, Lyme Disease Rashes and Look-alikes, CDC, last reviewed: October 9, 2020. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/rashes.html


[18] Moniuszko-Malinowska A, Czupryna P, Dunaj J, et al. Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis. Postepy Dermatol Alergol. 2018;35(5):490-494. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232541/


[19] Photo credit, Glatz M et al., Clinical Spectrum of Skin Manifestations of Lyme Borreliosis in 204 Children in Austria, Advances in Dermatology and Venereology, Vol 95, Issue 5, Nov 4, 2014. Retrieved from: https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2000


[20] Warshafsky S et al., Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis, Journal of Antimicrobial Chemotherapy, Volume 65, Issue 6, June 2010, Pages 1137–1144. Retrieved from: https://academic.oup.com/jac/article-pdf/65/6/1137/2086677/dkq097.pdf


[21] Nadelman R et al., Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite, N Engl J Med 2001; 345:79-84. Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJM200107123450201


[22] Photo Credit- Ticks Image Gallery, CDC, last reviewed: December 18, 2020. Retrieved from: https://www.cdc.gov/ticks/gallery/index.html


[23] Smith G et al., Management of Tick Bites and Lyme Disease During Pregnancy, J Obstet Gynaecol Can 2012;34(11):1087–1091. Retrieved from: https://www.jogc.com/article/S1701-2163(16)35439-1/pdf


[24] Treatment for erythema migrans, CDC, last reviewed: November 3, 2020. Retrieved from: https://www.cdc.gov/lyme/treatment/index.html


[25] Post-Treatment Lyme Disease Syndrome, CDC, last reviewed: November 8, 2019. Retrieved from: https://www.cdc.gov/lyme/postlds/index.html


[26] Ehrlichiosis Transmission, CDC,last reviewed: January 17, 2019. Retrieved from:https://www.cdc.gov/ehrlichiosis/transmission/index.html


[27] Ehrlichiosis Epidemiology and Statistics, CDC, last reviewed: March 26, 2020. Retrieved from: https://www.cdc.gov/ehrlichiosis/stats/index.html


[28] Ehrlichiosis Clinical and Laboratory Diagnosis, CDC, last reviewed: January 17, 2019. Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/diagnosis.html


[29] Ehrlichiosis Signs and Symptoms, CDC, last reviewed: January 17, 2019. Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/diagnosis.html


[30] Ehrlichiosis Treatment, CDC, last reviewed: January 17, 2019.Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/treatment.html


[31] Todd S et al., No Visible Dental Staining in Children Treated with Doxycycline for Suspected Rocky Mountain Spotted Fever, J Pediatrics 2015;166:1246-51. Retrieved from: http://www.jpeds.com/article/S0022-3476(15)00135-3/pdf?ext=.pdf


[32] Anaplasmosis Transmission, CDC, last reviewed: January 11, 2019. Retrieved from:https://www.cdc.gov/anaplasmosis/transmission/index.html


[33] Anaplasmosis Epidemiology and Statistics, CDC, last reviewed: March 26, 2020. Retrieved from: https://www.cdc.gov/anaplasmosis/stats/index.html


[34] Anaplasmosis Signs and Symptoms, CDC, last reviewed: January 11, 2019. Retrieved from: https://www.cdc.gov/anaplasmosis/symptoms/index.html


[35] Anaplasmosis Clinical and Laboratory Diagnosis, CDC, last reviewed: January 11, 2019. Retrieved from: https://www.cdc.gov/anaplasmosis/healthcare-providers/clinical-lab-diagnosis.html


[36] Anaplasmosis Treatment, CDC, last reviewed: January 11, 2019. Retrieved from: https://www.cdc.gov/anaplasmosis/healthcare-providers/treatment.html



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