Scope and Spread of Lyme Disease

Explore the widespread prevalence of Lyme disease beyond reported cases, delve into the tick life cycle, and learn about transmission risks and prevention strategies in endemic areas across the United States.

This article explores is part one of a four part CME series “Diagnosis and Treatment of Four Tickborne Diseases: Lyme Disease, Ehrlichiosis, Anaplasmosis and Babesiosis” .

LYME DISEASE (Part 1)

by Stuart M. Caplen, MD

Although there are only about 30,000 cases of Lyme disease reported to the CDC per year, the CDC estimates the actual total is about 476,000 cases per year in the United States.[2]

As can be seen on the map below, most cases of Lyme disease occur in the Mid-Atlantic states, New England and the Midwest, although there is significant distribution around the country. The geographic distribution of the three other tickborne infections under discussion can also be seen below.

Tick Life Cycle and Infection Transmission

Lyme disease is a tick transmitted disease, with protean manifestations, usually caused by the spirochete, Borrelia burgdorferi, although it can rarely be caused by Borrelia mayonii.

Ticks go through four life stages: egg, six-legged larva, eight-legged nymph, and adult. After hatching from the eggs, ticks must eat blood to survive. Ticks can take up to 3 years to complete their full life cycle, although the Ixodes scapularis tick, also known as the blacklegged or deer tick, that typically spreads Lyme disease has a 2-year life cycle. Most nymph infections occur in the spring and summer, with adult tick caused infections typically occurring during the cooler months. Nymph ticks are much harder to detect, as they are typically less than 2 mm in size, and may be more likely to feed unnoticed, as opposed to an adult tick.[4] For Lyme disease to occur, the tick needs to be attached for a significant time, typically 36-48 hours before an infection can be transmitted.[5] The more engorged the tick the higher the likelihood of an infection being transmitted.

Most tick bites do not result in Lyme disease infections. In some studies, only 2% to 3% of people bitten by ticks in endemic areas actually contract Lyme disease.[6,7]

Ixodes scapularis life and feeding cycle [4]

Ticks can detect an animal’s breath and sense body odors, heat, moisture, and vibrations. Ticks can’t fly or jump, but many tick species wait in a position known as “questing” on well walked paths. When questing, ticks hold onto leaves and grass by their third and fourth pair of legs and keep their first pair of legs outstretched. When a host brushes by the tick, it climbs aboard, and either attaches quickly or goes looking for places where the skin is thinner.

Ticks transmit pathogens that cause disease through the process of feeding. When the tick finds a feeding spot, it grasps the skin and cuts into the surface. The tick then inserts its feeding tube, which may have barbs to help keep the tick in place. Many species also secrete a substance that keeps them firmly attached to the host during the meal. Tick saliva contains an anesthetic like substance, to prevent the host from feeling the attached tick. A tick will then suck the host’s blood slowly for several days. If the host animal has a bloodborne infection, the tick can ingest the pathogens and become infective. If the tick’s saliva contains a pathogen, it may enter the host animal during feeding causing an infection. After feeding, most ticks will drop off the host and move on to the next life stage.[4]

[4]

How to Remove a Tick

Never crush a tick with your fingers. Use fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible. Pull upward with steady, even pressure. Don’t twist or jerk the tick, as this can cause the mouth-parts to break off and remain in the skin. If this happens, remove the mouth-parts with tweezers if they are easily removable. If a significant debridement is necessary, most sources recommend leaving the mouth parts in place. After removing the tick, thoroughly clean the bite area with rubbing alcohol or soap and water. Dispose of a live tick by putting it in alcohol, placing it in a sealed bag or container, wrapping it tightly in tape, or flushing it down the toilet.

Methods for tick removal that have been tried, but are not recommended include; applying a hot match or nail to the tick, covering the tick with petroleum jelly, nail polish, alcohol or gasoline, using injected or topical lidocaine, or passing a suture needle through the tick.[8,9]

Tick removal technique [8]

Should You Send the Removed Tick for Laboratory Testing?

It may be helpful diagnostically to identify which tick a patient has been bitten by, either with identification by the clinician, or sending the tick to a laboratory for identification.[10,11]

Testing if a tick is carrying B. burgdorferi is not recommended, for the following reasons:

• Positive results showing that the tick contains a disease-causing organism do not necessarily mean that it caused an infection.

• Negative results can lead to false assurance, as the patient may have unknowingly been bitten by another infected tick as well.

• Clinical symptoms will typically occur prior to the test results returning.

• Laboratories that conduct tick testing are not required to have the same standards of quality control used by clinical diagnostic laboratories, potentially leading to misdiagnosis.[10]

Lyme Disease Testing

Testing for Lyme disease is both complicated, and potentially inaccurate. Currently a 2-tier antibody assay method is the recommended testing method. This has a sensitivity of only 30%–40% during the typical 30-day window period of early infection, while the antibody response is developing. The 2-tier method does have a 70%–100% sensitivity for disseminated disease. Specificity of 2-tier testing is >95% during all stages of Lyme disease.[12]

In 2-tier Lyme disease antibody testing, a screening test is done either using an enzyme immunoassay or immunofluorescence assay. If the screening test is negative another diagnosis should be considered, or the test may have been done during the 30-day antibody window period, before enough antibody has been produced to be detected, and repeat testing may be needed later on. If the screening test is positive or equivocal, immunoglobulin G(IgG) and or immunoglobulin M(IgM) western blot tests are confirmative. If symptoms are less than 30 days both IgG and IgM western blot tests are recommended, with IgM being the acute phase antibody first produced, and IgG the later phase and longer lasting antibody. Theoretically, if symptoms have been present for over 30 days only the IgG western blot is needed, but most labs routinely test for both.[14]

The western blot is an immunoassay that allows visualization of Borrelia antibodies in specific bands. The IgM western blot is considered positive if two of three antibody bands measured are positive. An IgG western blot is positive if five of the ten antibody bands measured are positive. It is important to avoid interpreting fewer bands as evidence of infection because some of the antibodies tested for are cross-reactive with non-Borrelial antigens. Therefore, presence of one IgM band or less than five IgG bands does not indicate an overall positive result. Overinterpreting a small number of antibody bands leads to reduced specificity and potential misdiagnosis.[10,12]

Polymerase chain reaction(PCR) testing can provide highly specific evidence of B. burgdorferi nucleic acid in synovial fluid, skin biopsy tissue, blood, and cerebral spinal fluid(CSF). However, its clinical utility is limited by low sensitivity, particularly for blood and CSF samples. Studies of PCR on blood have found that its high specificity is outweighed by its lack of clinical sensitivity and potential for contamination, and as a result, PCR testing of blood or CSF for Lyme disease is not recommended.[12]

For CSF infections, obtaining simultaneous samples of CSF and serum for determination of anti-Borrelia antibodies allows for calculation of the CSF:serum antibody index. This test can differentiate between intrathecal synthesis versus passive diffusion of specific anti-Borrelia antibodies into the CSF.[10,13]

Because B.burgdorferi is a slow-growing organism and current culturing methods are labor-intensive and have poor sensitivity, culture is generally not recommended. Routine hospital blood cultures will not grow B.burgdorferi.[10]

It is not recommended to perform Lyme disease testing in asymptomatic patients after a tick bite, as an infection may be too early to detect, and even if delayed testing is done 4-6 weeks later there is insufficient evidence that patients with asymptomatic seropositivity should receive antibiotic therapy.[10]

Symptoms of Early Lyme Disease [15]

• Possible symptoms of early Lyme disease include fever, chills, headache, fatigue, muscle and joint aches, and swollen lymph nodes.

• A small bump or redness at the site of a tick bite that occurs immediately and resembles a mosquito bite is common. This generally goes away in 1-2 days and is not a sign of Lyme disease.

• The erythema migrans rash occurs in approximately 70 to 80 percent of infected persons. It begins at the site of a tick bite after an average delay of 7 days but onset can range from 3 to 30 days. It typically has a bullseye appearance, but may present with central sparing or complete central involvement.[15A]

[16]

Possible Signs and Symptoms of Disseminated Lyme Disease [15]

Musculoskeletal/Rheumatological

• Intermittent pain in tendons, muscles, joints, and bones

• Arthritis with severe joint pain and swelling, particularly the knees and other large joints.

• Baker’s cyst

Neurologic

• Bell’s palsy or other cranial neuropathies

• Headache, meningitis, or rarely encephalitis

• Motor and sensory radiculoneuropathy, mononeuritis multiplex

• Problems with short-term memory and cognitive problems

Multiple truncal erythema migrans lesions [17]

Cardiac

• Lyme carditis- leading to heart block, myocarditis, or pericarditis

Dermatologic

• Multiple erythema migrans lesions

• Acrodermatitis chronica atrophicans

• A rash that can potentially be seen in chronic Lyme disease, especially on the dorsal surfaces of the hands, feet, knees, and elbows. Initially the rash is erythematous, followed by discoloration, inflammation and potentially skin atrophy.

Acrodermatitis chronica strophicans of the hand [18]

• Borrelial lymphocytoma

• Borrelial lymphocytoma is an uncommon manifestation of early disseminated Lyme disease reported only in Europe, possibly due to infection by other Borrelia strains more common there. It is a bluish-red nodular swelling that typically occurs on the ear lobe in children, or on the breast in adults.

Borrelial lymphocytoma of the earlobe [19]

Recommended Treatment for Lyme Disease Antibiotic Prophylaxis

Prophylactic antibiotic therapy is recommended for adults and children within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal or low risk.

One meta-analysis concluded that there was a 2.2% chance of getting Lyme disease in untreated patients, compared to 0.2% infection rate in the antibiotic prophylaxis group.[21] A prospective study of prophylactic antibiotics after tick bites found a 3.2% infection rate in the placebo group and a 0.4% infection rate in the antibiotic prophylaxis group.[22]

A tick bite is considered to be high-risk only if it meets these three criteria:

1. The tick bite was from an identified Ixodes vector species.

2. The tick bite occurred in a highly endemic area

3. The tick was attached for ≥36 hours. The duration of tick attachment is an important predictor of subsequent Lyme disease. Unfed or flat recently attached ticks do not pose a significant risk for Lyme disease. The likelihood of transmission increases with the duration of attachment and the majority of transmission occurs after 36–48 hours of attachment.[10]

Nymphal Blacklegged Tick after Feeding [22]

For high-risk tick bites in all age groups, a single dose of oral doxycycline within 72 hours of tick removal is recommended. Doxycycline is given as a single oral dose, 200 mg for adults and 4.4 mg/kg (up to a maximum dose of 200 mg) for children. There is no study of the efficacy of doxycycline in children under 12 years of age and the parents should understand that monitoring for symptoms and signs is important.

Doxycycline is contraindicated in pregnancy, and the recommendation for tick bites during pregnancy most commonly is watchful waiting and treating if Lyme disease occurs, rather than using prophylaxis. Amoxicillin in a 10-day course might work for prophylaxis in the pregnant patient, but is not recommended because the frequency of adverse reactions is higher than the Lyme disease cases it prevents.[23] The latest Lyme disease prophylaxis during pregnancy recommendation of 3 different professional societies, which includes the Infectious Diseases Society of America is this: “Because of uncertainty about the safety of doxycycline in pregnancy, we advise pregnant women to have an informed discussion with their physicians about the risks, benefits, and uncertainties of antibiotic treatment versus observation.”[10]

Please note that while amoxicillin and cefuroxime are not recommended currently for prophylaxis, due to a lack of data, they can be used for treatment of early Lyme disease.

Recommended Treatment of Erythema Migrans Rash/Early Lyme Disease

Doxycycline, amoxicillin, or cefuroxime are recommended as treatment for erythema migrans rash/early Lyme disease. The dosage and duration are listed in the table below.

NOTE: For people intolerant of amoxicillin, doxycycline, and cefuroxime, the macrolides azithromycin, clarithromycin, or erythromycin may be used, although they have a lower efficacy. People treated with macrolides should be closely monitored to ensure that symptoms resolve. [24]

Additional considerations for treating erythema migrans rash/early Lyme disease include:

• In the pregnant patient or woman who wants to continue breast feeding, amoxicillin would be the first drug of choice.

• In infants and children, amoxicillin or cefuroxime can be used to avoid the use of doxycycline.[10]

• If azithromycin is used, the indicated duration is 5–10 days, with a 7-day course being the most common one prescribed most commonly [10].

• In patients with acrodermatitis chronica atrophicans, oral antibiotic therapy for 21–28 days is recommended.[12]

• In patients with borrelial lymphocytoma, oral antibiotic therapy for 14 days is recommended.[10]

• Coinfection should be investigated in patients who have a persistent fever while on antibiotic treatment for Lyme disease. If fever persists despite treatment with doxycycline, Babesia microti infection is an important consideration.[10]

For more information on the CDC recommended antibiotic regimes for Lyme carditis/heart block, arthritis or neurologic Lyme disease, some of which may require intravenous antibiotics as initial therapy, go to this link; https://www.cdc.gov/lyme/treatment/index.html . For more information on the specific treatment of Lyme disease complications, such as heart block, go to this link; https://www.idsociety.org/practice-guideline/lyme-disease/ .

Post-Treatment Lyme Disease

Although most cases of Lyme disease can be cured with a 10-day to 4-week course of oral antibiotics, patients can sometimes have symptoms of pain, fatigue, or difficulty thinking that lasts for more than 6 months after they finish treatment, called Post-Treatment Lyme Disease Syndrome (PTLDS). It has been hypothesized that the syndrome is caused by an autoantibody response. There is no proven treatment for PTLDS, and studies have found that prolonged antibiotic treatment works no better than patients who received placebo. Patients with PTLDS usually get better over time, but it can take many months to feel completely well.[10,25]

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REFERENCES

[1] Lyme Disease, CDC, last reviewed: February 24, 2021. Retrieved from: https://www.cdc.gov/lyme/index.html

[2] Lyme Disease, Data and Surveillance, CDC, last reviewed January 14, 2021. Retrieved from: https://www.cdc.gov/lyme/datasurveillance/index.html

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

[4] How ticks spread disease, CDC, last reviewed: September 21, 2020. Retrieved from: https://www.cdc.gov/ticks/life_cycle_and_hosts.html

[5] Lyme Disease Transmission. CDC, last reviewed January 29, 2020. Retrieved from: https://www.cdc.gov/lyme/transmission/index.html#:~:text=Ticks%20can%20attach%20to%20any,disease%20bacterium%20can%20be%20transmitted

[6] Hofhuis, A et al., Predicting the risk of Lyme borreliosis after a tick bite, using a structural equation model. PloS one vol. 12,7 e0181807. 24 Jul. 2017. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524385/

[7] Nadelman RB 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, July 12, 2001. Retrieved from: https://www.nejm.org/doi/full/10.1056/nejm200107123450201

[8] Tick removal and testing, CDC, last reviewed April 22, 2019. Retrieved from: https://www.cdc.gov/lyme/removal/index.html

[9] Gammons M, Salam G, Tick Removal, Am Fam Physician. 2002 Aug 15;66(4):643-646. Retrieved from: https://www.aafp.org/afp/2002/0815/p643.html#afp20020815p643-b7

[10] Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease, Clinical Infectious Diseases, November 30, 2020. Retrieved from: https://www.idsociety.org/practice-guideline/lyme-disease/

[11] Tick removal and testing, CDC, last reviewed: April 22, 2019. Retrieved from: https://www.cdc.gov/lyme/removal/index.html

[12] Moore, Andrew et al. “Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States.” Emerging infectious diseases vol. 22,7 (2016): 1169–1177. Retrieved from https://wwwnc.cdc.gov/eid/article/22/7/15-1694_article

[13] Theel, Elitza S et al., “Limitations and Confusing Aspects of Diagnostic Testing for Neurologic Lyme Disease in the United States.” Journal of clinical microbiology vol. 57,1 e01406-18. 2 Jan. 2019. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322465/

[14] Two-tiered Testing Decision Tree, CDC, last updated: November 15, 2011. Retrieved from: https://www.cdc.gov/lyme/healthcare/clinician_twotier.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