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Ehrlichiosis: A Tick-Borne Threat

Understanding Ehrlichiosis: Symptoms, Diagnosis, and Treatment


Ehrlichiosis, caused by bacteria carried by ticks, presents varying symptoms and requires prompt diagnosis and treatment. What you need to know to understand Ehrlichiosis symptoms, disgnosis, and treatments.



EHRLICHIOSIS (Part 2)



Ehrlichiosis is caused by three bacteria, Ehrlichia chaffeensis, Ehrlichia ewingii, or Ehrlichia muriseauclairensis. The majority of reported cases are due to infection with E. chaffeensis. E. chaffeensis and E. ewingii are carried by the lone star tick, Amblyomma americanum, found primarily in the south-central and eastern United States. E. muris eauclairensis is carried by the blacklegged tick, Ixodes scapularis, but despite this tick’s wide distribution has only been reported in Wisconsin and Minnesota.[26] In 2018, there were 1,799 cases of E. chaffeensis reported to the CDC. The other Ehrlichia infections are much rarer, with only 218 cases of E. ewingiiehrlichiosis reported to CDC from 2008–2018, and about 115 cases of ehrlichiosis caused by E. muris eauclairensis reported since its discovery in 2009.[27]


ehrlichiosis map of activity
[3]

Ehrlichia are small, gram-negative bacteria, round or ellipsoidal in shape. They preferentially invade monocytes, macrophages, and neutrophils. In all of these cell types they occupy cytoplasmic vacuoles, usually in bacterial microcolonies known as morulae.[28]


Morula inside a monocyte
Morula inside a monocyte [15]

Early Signs and Symptoms of Ehrlichiosis [29]

Signs and symptoms of ehrlichiosis typically begin within 5 to 14 days after the bite of an infected tick.


Early signs and symptoms are usually mild or moderate and may include:

  • Fever, chills

  • Severe headache

  • Muscle aches

  • Nausea, vomiting, diarrhea, loss of appetite

  • Gastrointestinal symptoms are less common in patients with E. ewingii ehrlichiosis than with the other two species.

  • Confusion

  • Rash

  • A rash develops in up to 60% of children, and less than 30% of adults, and typically begins about 5 days after symptom onset.

  • The rash usually spares the face, but in some cases may spread to the palms of hands and soles of feet.

  • The rash associated with E. chaffeensis infection may range from maculopapular to petechial in nature and is usually non-pruritic.

  • Rash is infrequent in cases of E. muris eauclairensis.


Late Symptoms of Ehrlichiosis[29]

If treatment is delayed and the ehrlichiosis infection is allowed to continue, the disease may become severe. Severe illness may involve:

  • Meningitis, meningoencephalitis, and other central nervous system involvement (20% of patients)

  • Acute respiratory distress syndrome

  • Toxic shock-like or septic shock-like syndromes

  • Renal failure

  • Hepatic failure

  • Coagulopathies


E.chaffeensis generally is the more serious illness, as neither E. ewingii nor E. muris eauclairensis infections have been associated with fatalities. The case fatality rate of E. chaffeensis is about 1%.


Laboratory Findings in Ehrlichiosis[28]

  • General laboratory findings in ehrlichiosis can include absolute leukopenia, thrombocytopenia, and moderately elevated hepatic transaminases.

  • Anemia is reported in about half of patients, but generally occurs later in the course of the illness.


Immunohistochemical stain demonstrating Ehrlichia chaffee morulae (red) within monocytes in the kidney
Immunohistochemical stain demonstrating Ehrlichia chaffee morulae (red) within monocytes in the kidney [15]

Testing for Ehrlichiosis[29]

Microscopic examination of a blood smear may reveal morulae, which are microcolonies of Ehrlichiae in the cytoplasm of white blood cells. E. chaffeensis most commonly infects monocytes while E. ewingii more commonly infects granulocytes. No specific target cell has been identified for E. muris eauclairensis. A concentrated buffy-coat smear can improve the yield of morulae evaluation compared with a standard blood smear. When positive, the diagnosis can be made relatively easily, but unfortunately blood smear examination is relatively insensitive for detecting the disease. If a bone marrow biopsy is performed as part of the investigation of cytopenias, immunostaining the bone marrow biopsy specimen to look for morulae, may help diagnose ehrlichiosis. Organ biopsies, if done for other purposes may also show evidence of morulae.


The indirect immunofluorescence antibody (IFA) assay for IgG, is the test most widely performed to diagnose ehrlichiosis. IgG IFA assays should be performed on paired acute and convalescent serum samples collected 2–4 weeks apart with a fourfold increase or decrease in the titers needed to be interpreted as positive. Antibody titers are frequently negative in the first week of illness. Ehrlichiosis cannot be confirmed using a single acute set of antibody results. IgM IFA assays are also offered by reference laboratories but are not necessarily indicators of acute infection, and appear to be less specific than IgG antibodies. It is therefore not recommended to use IgM antibody titers alone for diagnosis.


Polymerase chain reaction (PCR) amplification can be performed from whole blood specimens. PCR is most sensitive in the first week of illness and decreases in sensitivity following the administration of appropriate antibiotics (within 48 hours). Although a positive PCR result is helpful, a negative result does not rule out the diagnosis, and treatment should not be withheld due to a negative result if ehrlichiosis is clinically suspected. PCR may also be used to amplify DNA in solid tissue and bone marrow specimens.


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


Treatment of Ehrlichiosis [30]

As opposed to Lyme disease, post-tick bite antibiotic prophylaxis is currently not recommended to prevent ehrlichiosis.


Doxycycline is the treatment of choice for ehrlichiosis if the diagnosis is suspected, for patients of all ages, including children <8 years. Doxycycline is most effective at preventing severe complications from developing if started within the first week of illness.


The recommended dosage for is doxycycline for adults is 100 mg every 12 hours, and for children under 45 kg (100 lbs.) the dose is 2.2 mg/kg body weight given twice a day. Dental staining in children has been a concern with doxycycline, but a study of 58 children under eight years of age with Rocky Mountain spotted fever, found no evidence of dental staining from doxycycline treatment.[31] Patients with suspected ehrlichiosis should be treated with doxycycline for at least 3 days after the fever subsides, and there is evidence of clinical improvement, typically in 5-7 days.


In cases of life-threatening allergies to doxycycline, severe doxycycline intolerance, and in some pregnant patients for whom the clinical course of ehrlichiosis appears mild, physicians might consider alternate antibiotics. Rifampin appears effective against E. chaffeensis in a laboratory setting, but has not been evaluated as an alternative therapy in a clinical setting. Caution is advised when exploring treatments other than doxycycline, as other tickborne co-infections like Lyme disease or Rocky Mountain spotted fever may go intreated. An infectious disease consult is recommended when treating the pregnant patient.



 

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


Lyme disease, Ehrlichiosis, Anaplasmosis and Babesiosis" 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


initially published 2021.



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