Lyme Disease: The Forgotten Vector-Borne Disease of North Carolina

By Katherine S. Adams, William J. Taylor, Peter Ahiawodzi, and Mark Moore

of the 230 cases of Lyme disease in 2016 were recorded in Wake County. (1) The number of cases in Wake County is quite disturbing as it is one of the fastest growing areas in the nation and second-most populous county in North Carolina with approximately 1,025,000 residents. (7)

Symptoms

Background

Transmitted by blacklegged ticks (species: Ixodes Scapularis; family: Ixodidae), Lyme disease is a multisystem bacterial infection caused by the spiral-shaped bacterium, Borrelia burgdorferi. It is important to note that blacklegged ticks are commonly referred to as “deer ticks.” First documented in 1975 as childhood arthritis, Lyme disease received its name from the small town of Lyme, Connecticut. According to the Centers for Disease Control and Prevention (CDC), Lyme disease is the most commonly reported vector-borne illness in the United States and was the fifth most common nationally notifiable disease in 2014.(1)

Even though the majority of cases are reported in the northeast and north central states, in recent years, the geographical magnitude of disease has expanded raising the prospect of Lyme disease becoming endemic in the southeast. (2) Recent research suggests that regions across the United States where Lyme disease was previously uncommon are now experiencing a growth in blacklegged tick populations (Appendix A). (3) Ominously, people living in these newly affected areas may be unaware of the associated health risks and appropriate prevention techniques since they previously had no reason to worry. (3)

Data from the CDC indicates the state of North Carolina is experiencing a drastic increase in the number of Lyme disease cases per year (Appendix B). (1) For surveillance purposes, five counties within the state were classified as endemic for Lyme disease in 2015: Alleghany, Haywood, Guilford, Wilkes and Wake. (4,5) For a county to be classified as endemic there must be at least two confirmed cases of Lyme disease acquired within the county or a population of infected blacklegged ticks must have been previously documented within the county. (6) According to the CDC, 27 Symptoms of Lyme disease resemble other common illnesses, thus making diagnosing arduous; however, there is one characteristic symptom associated with Lyme disease, the “bull’s eye” rash (erythema migrans). Located at the site of attachment, the small circle grows over time reaching the dimension of a penny or larger. Other symptoms that often co-occur with the rash include: fatigue, chills, fever, headache, lymphadenopathy, neck stiffness, myalgia, and arthralgia. (8) Lyme disease has three clinical stages: early-localized, earlydisseminated, and late Lyme disease. Early symptoms usually occur 3 to 30 days following the tick bite. The rash, erythema migrans (EM), is characterized within the first stage of early-localized Lyme disease. (9) Multiple EM, as well as cardiac and neurological findings, are often observed in the early-disseminated stage of the illness. Cardiac findings include carditis with second-or third-degree heart block, while neurologic findings include cranial neuritis, lymphocytic meningitis, or mo-

tor/sensory radiculoneuritis. (9) In late Lyme disease, patients typically suffer from rheumatologic complications that can be intermittent or chronic; with the knees being the most commonly affected joints. (9,10)

Diagnosis

Diagnosing Lyme disease is often extremely challenging for physicians if an individual infected with the disease does not develop a rash or show signs of a tick bite and only presents flulike symptoms. If EM is not present, but the patient shows other symptoms, then serologic testing analyzing blood samples for antibodies can be completed to confirm the diagnosis. (11)

Following the initial infection, several weeks are needed for the antibodies to build to measurable levels before serologic testing can be conducted. (11) Even though false-positives occasionally occur, the CDC recommends two-tiered serologic testing. The enzyme-linked immunosorbent assay (ELISA) is conducted first, followed by a western blot. If patients present with nonspecific symptoms and have no history of tick exposure in Lyme-endemic areas, serologic testing is not recommended. (12)

When diagnosing Lyme disease, clinicians typically rely on patient history and physical examination, with consideration given to the time of year, work and living environment, locations recently visited, and common recreational activities. (12) Most people who are diagnosed with Lyme disease do not recall being bitten by a tick. (3) Unfortunately, the most common reason for failure of treatment is misdiagnosis by clinicians.

Prophylaxis and Treatment

The sooner Lyme disease is diagnosed and treated, the greater probability of complete recovery. Once an attached tick has been removed, prophylaxis may be considered in the following cases: 1) all patients, 2) only patients believed to be at an increased risk for developing Lyme disease (especially attachment of more than 36 hours), 3) patients who develop EM or other clinical symptoms, and 4) all patients who seroconvert from a negative to a positive serum antibody test result. (14)

National treatment guidelines for Lyme disease published by the Infectious Diseases Society of America (IDSA) advise either 100 mg of doxycycline twice per day, 500mg of amoxicillin three times per day, or 500 mg of cefuroxime twice per day(See Appendix C). (13,14) These agents are inexpensive and seldom cause any serious adverse side effects. (13) If the patient cannot take medication orally, then 2 grams of ceftriaxone is recommended parenterally once per day. (14) The recommended duration of therapy for either oral or parenteral administration is 14 days. (14) When treated with antibiotics, early-localized and early-disseminated Lyme disease is eliminated in 90% of infected patients. (12) While more serious symptoms of early-disseminated Lyme disease can be treated with antibiotics, arthritis seen in the late stages of Lyme disease is often impossible to eradicate with antibiotics alone. Unfortunately, an estimated 20% of patients do not recover following antibiotic treatment and continue to experience chronic arthritis symptoms. (16)

Prevention, Patient Education, and the Role of the Pharmacist

The pharmacist can serve to educate people in the prevention of Lyme disease (Appendix D). The best method to control and prevent Lyme disease occurrence is for individuals to avoid blacklegged ticks and their natural habitats; however, for individuals who live and work in endemic areas, it is imperative that insect repellants containing the chemical DEET or the insecticide permethrin be applied to clothing. (11) The concentration of DEET ranges from less than 10 percent to over 30 percent; however, concentrations of more than 30 percent are not recommended for children. (17) The duration of protection increases as the concentration of DEET increases. (17) DEET has been proven to be a nontoxic and efficient means of

Providing education on the importance of wearing lightcolored clothing as well as tick identification and prompt removal (e.g., within the first 24 hours of attachment) can reduce the risk of infection. (12) The tick should be grasped with tweezers as close to the skin as possible, and then pulled away from the site of attachment steadily until detached (Appendix E). (11) A study conducted in Connecticut demonstrated that body checks within 36 hours and baths within 2 hours following exposure are effective strategies in reducing the risk of Lyme disease. (18)

Pets (e.g., cats and dogs) also serve as host for Ixodes scapularis in high-risk areas. Treating pets with a tick-preventative can reduce the risk of encountering an infected tick. (19)

Patient education on common symptoms of Lyme disease can also increase awareness and help patients to get prompt medical attention. Furthermore, when antibiotic therapy is initiated, the pharmacist can play a critical role in educating the patient about the importance of medication adherence and potential adverse side effects. (16)

The annual update released by the State Epidemiologist and the Head of the Communicable Disease Branch encourages providers to be mindful of the patients who present with symptoms of the disease. North Carolina residents must be made aware of appropriate prevention techniques. While the mortality rate for Lyme disease is low, its lingering symptoms can be quite debilitating.

Katherine S. Adams is a Doctor of Pharmacy Candidate, MSPH Candidate, and MBA Candidate at the Campbell University College of Pharmacy & Health Sciences. William J. Taylor, PharmD, is an Associate Professor of Public Health at the Campbell University College of Pharmacy & Health Sciences. Peter Ahiawodzi, PhD, MPH, CPH, is an Assistant Professor of Epidemiology at the Campbell University College of Pharmacy & Health Sciences. Mark Moore, PharmD, MS, MBA is an Associate Dean for Student Affairs & Admissions at the Campbell University College of Pharmacy & Health Sciences. taylorw@campbell.edu

References

1. Centers for Disease Control. Lyme disease. Accessed on June 22, 2018. URL: https:// www.cdc.gov/lyme/index. html.

2. Lantos M, Pan K, Gaines N, et al. Geographic Expansion of Lyme Disease in the Southeastern United States, 2000-2014. Open Forum Infectious Diseases. 2015.

3. Foster H. Ticks that Transmit Lyme Disease Reported in 48.6% of U.S. Counties. Entomology Today. 2016. URL: https://entomologytoday. org/2016/01/18/ticks-thattransmit-lyme-disease-reported-in-fifty-percent-of-u-scounties/.

4. Paul M. Lantos, Lise E. Nigrovic, Paul G. Auwaerter, Vance G. Fowler Jr., Felicia Ruffin, R. Jory Brinkerhoff, et el., Geographic Expansion of Lyme Disease in the Southeastern United States, 2000–2014. Open Forum Infectious Diseases, December 2015, Volume 2, Issue 4. https://doi.org/10.1093/ofid/ ofv143

5. Davies, M. (2015). Annual Update on Surveillance for Lyme Disease in North Carolina. Retrieved from https:// www.buncombecounty.org/ common/health/nc-dhhs-annual-update-on-surveillancefor-lyme-disease-in-northcarolina.pdf 6. Centers for Disease Control. (2011). Lyme Disease 2011 Case Definition. Accessed on July 16, 2018. Retrieved from https://wwwn.cdc.gov/ nndss/conditions/lyme-disease/case-definition/2011/.

7. Walston S. Learn About Wake County. Accessed on June 22, 2018. URL: http:// www.wakegov.com/about/ facts/Pages/default.aspx. 8. Mead P. Epidemiology of Lyme Disease. Infectious Disease Clinics of North America. URL: https://www. id.theclinics.com/article/ S0891-5520(15)00024-0/abstract.

9. Johnson, M. (2010). Chronic Lyme Disease: A Survey of Connecticut Primary Care Physicians. J Pediatr, 157(6), 1025-1029.e2. doi:10.1016/j. jpeds.2010.06.031

10. Jen C, Dorado V, Lu B, Nguyen S. Lyme Disease: The Pharmacist’s Role in Treatment and Prevention. U.S. Pharmacist. 2016. URL: https://www.uspharmacist.com/article/lyme-disease-the-pharmacists-rolein-treatment-and-prevention. 11. Tran M, Waller L. Effects of Landscape Fragmentation and Climate on Lyme Disease Incidence in the Northeastern United States. EcoHealth. 2013; 2014;10(4):394-404. 12. Ziegler M, Didas M, Smith S. Diagnosing and Managing Lyme Disease. Journal of the American Academy of Physician Assistants. 2013;26(11):21-26. 13. Hayes B, Piesman J. How Can We Prevent Lyme Disease? N Engl J Med. 2003;348(24):24242430. URL: https://doi. org/10.1056/NEJMra021397. 14. Infectious Disease Society of America. (2007). The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis. Accessed on June 28, 2018. Retrieved from http://www. idsociety.org/Guidelines/Patient_Care/IDSA_Practice_ Guidelines/Infections_By_ Organism-28143/Bacteria/ Lyme_Disease/ 15. Centers for Disease Control and Prevention. (2017). Research on Doxycycline and Tooth Staining. Accessed on July 16, 2018. Retrieved from https://www.cdc.gov/ rmsf/doxycycline/index.html 16. Knisley J, Johnson M. Lyme disease: Knowledge is the Best Prevention. Nurse Pract. 2004;29(8):34-43. 17. North Carolina Department of Health and Human Services. (2018). Safe Use of Insect Repellents. Accessed on July 16, 2018. Retrieved from http://epi.publichealth. nc.gov/cd/diseases/deet.html 18. Brisson D, Dykhuizen E, Ostfeld S. Conspicuous Impacts of Inconspicuous Hosts on the Lyme Disease Epidemic. Proceedings of the Royal Society B: Biological Sciences. 2008;275(1631):227-235. 19. Hamer A, Tsao I, Walker D, Mansfield S, Foster S, Hickling J. Use of Tick Surveys and Serosurveys to Evaluate Pet Dogs as a Sentinel Species for Emerging Lyme Disease. J Am Vet Med Assoc. 2009;234(2):244-244. 20. New Era Pest Control Inc. How to Remove a Tick. Accessed on June 28, 2018. Retrieved from http://www. newerapestcontrol.com/ web/2014/07/01/remove-tick/

Appendix A (Reference 4) The first map (A) reveals I. scapularis distribution in 1998,0 and the second map (B) reveals distribu-

tion in 2015. Counties reporting six or more ticks were classified as established (red and green) and counties reporting at least one tick were classified as reported (blue and yellow).

The graph shows the increasing incidence of Lyme disease cases from 2010 to 2016 in the state of North Carolina.

Appendix C (Reference 14) Infectious Disease Society of America guidelines for treating Lyme disease.

Preferred Oral Regimens for Treating Lyme Disease Drug Dosage Dosage (Pediatrics) Duration of Therapy (Adults & Pediatrics)

Amoxicillin 500 mg BID 50 mg/kg TID

14 (14-21) days Doxycycline 100 mg BID If > 8 yo, 4 mg/kg BID 14 (14-21) days

Cefuroxime

Axetil

500 mg BID 30 mg/kg BID 14 (14-21) days

Preferred Parenteral Regimens for Treating Lyme Disease Ceftriaxone 2 g Daily 50-75 mg/kg Daily 14 (10-28) days

Opportunities for the Pharmacist

• Increase awareness of tick-borne illnesses

• Counsel on potential risks of Lyme disease • Make recommendations for preventive measures o Bug-repellent clothing (ex. ElimiTick™, Insect Shield©, etc.) o Repellent selection for clothing applications (i.e. Permethrin) o Repellent selection for skin application (i.e. DEET)

• Educate on proper tick removal technique and storage for testing • Monitor post-exposure for early identification of a tick-associated rash • Provide assistance with early referral to a physician provider • Assist providers with selection of appropriate therapeutic management • Counsel on importance of medication adherence, drug-drug and drug-food interactions, and possible adverse events (e.g. photosensitivity)

• Recognition symptoms of Lyme disease at all stages of progression

Appendix E (Reference 20)