Ticks and Transmission Materials

TICKS AND TRANSMISSION: NASTY LITTLE BUGS NASTIER DISEASE

JEANNETTE Y. WICK, RPh, MBA, FASCP

Jeannette Y. Wick is the Director of the Office of Pharmacy Professional Development at the University of Connecticut.

Topic Overview

The various types of ticks across the United States have the potential to cause several diseases. The incidence of tick-borne diseases more than doubled between 2004 and 2016. Many of these diseases have similar non-specific symptoms, and misdiagnosis or delayed diagnosis is common. While prevention is the best approach to these diseases, they still occur with alarming frequency. Pharmacists and pharmacy technicians who know how to identify the different tick-borne diseases and can differentiate them can help patients and the healthcare team find diagnoses and treat them appropriately. For most (but not all) tick-borne diseases, doxycycline is the drug of choice for treatment.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-24-026-H01-P

Pharmacy Technician  0669-0000-24-027-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: March 12, 2024 Expiration Date: March 12, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians
 

How to Earn Credit: From March 12, 2024, through March 12, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Describe the types and symptoms of tick-borne infections

Identify each infection’s treatment based on CDC guidelines

Recall counseling points for patients and advice for prescribers

Disclosures

The following individuals were involved in developing this activity: Jeannette

Y. Wick, RPh, MBA, FASCP, and Pamela Sardo, PharmD, BS. Pamela Sardo and Jeannette Y. Wick have no conflicts of interest or financial relationships regarding the subject matter discussed. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

© RxCe.com LLC 2024: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

Ticks and Transmission: Nasty Little Bugs, Nastier Disease Introduction

Various types of ticks transmit infectious pathogens known as vector- borne diseases. Lyme disease is the most common vector-borne disease, but other tick-borne diseases, Rocky Mountain Spotted Fever, anaplasmosis, babesiosis, ehrlichiosis, and tularemia, also pose serious threats to human health. Alpha-gal syndrome has also emerged as a health threat. It is not an infection but a serious allergy that develops after a tick bite in some people. This continuing education activity discusses these other, less common tick- borne diseases, their symptoms, and appropriate treatments, as well as alpha- gal syndrome.

An Overview of Ticks and Tick-borne Illnesses

Ticks are interesting little arachnids (joint-legged arthropods), and they cause much human suffering. First discovered as vectors in disease transmission in 1906,1 they are associated with at least 12 different human diseases in the United States, identified in Table 1 below.3

The incidence of tick-borne diseases more than doubled between 2004 and 2016.2 While Lyme disease made up approximately 82% of tickborne cases in the United States, spotted fever rickettsioses, babesiosis, anaplasmosis, and ehrlichiosis cases also increased.2

POINT TO PONDER:

Why is it important to know about tick-borne diseases in your areas of the United States?

Many diagnosticians have a low index of suspicion for tick-borne diseases because of their vague symptoms and the possibility of coinfection. Overall, 39% of patients will be co-infected with more than one tick-borne organism.4 If patients are receiving appropriate treatment for Lyme disease but continue to experience fever for more than 24 hours or have unexplained thrombocytopenia and/or anemia, clinicians should suspect co-infection with other tick-borne illnesses.5 The most common co-infection with Lyme disease is babesiosis, and a small number of patients (less than 5%) will have triple infections (usually Lyme plus anaplasmosis and babesiosis).6 Disease severity tends to be worse in patients with co-infection, and symptoms may last longer. Older age and a history of splenectomy are risk factors for more severe illness in coinfection.5

Table 1

Tick-borne Diseases that Occur in the United States3

Why Do We Need Ticks

This section asks, “Why do we need ticks?” In other words, if we could eradicate ticks, what would change except the elimination of tick-borne disease? Ticks, like most other organisms, have assigned places in the ecosystem.7,8 Amphibians, birds, reptiles, wild turkeys, and various other animals consume ticks. Opossums are inordinate consumers of ticks and devour them relentlessly, as do guinea fowl. Scientists also track tick activity to monitor ecosystem status and changes. Abundant tick populations are usually associated with healthy populations of small mammals like rodents, squirrels, and rabbits. If tick populations decline, it can be an indication that small animals’ predators may be over-abundant. Tick populations also track climate change. Warming temperatures are more hospitable for ticks and their animal hosts, creating opportunities for ticks to spread diseases. As the temperature rises, ticks multiply.7,8 Recently, scientists have used ticks to analyze levels of environmentally persistent, ubiquitous pollutants called PFAS (per- and polyfluoroalkyl substances from plastics) because ticks “visit” many species and accumulate PFAS. They are sentinels of PFAS contamination.9

How Pathogens Modify Tick Behavior

Various types of ticks transmit infectious pathogens to other living organisms; in this capacity, ticks are called vectors.10 Ticks are sedentary predators that employ a position known as questing to find prey. They grip leaves, grass, or underbrush using their third and fourth pair of legs, holding their first pair of legs outstretched.11,12 Hosts that brush against the waiting tick become the tick’s prey.

The tick’s lifespan from birth to death is short, usually spanning two to three years and progressing through egg, larval, nymph, and adult stages.13 Their survival during the larval and nymph stages requires a new host for a blood meal for growth to the next stage. Adult females need a blood supply to produce eggs. Nymphal and larval forms of the Ixodes tick rely on the white-footed mouse for nourishment, while adult ticks feed on deer. Black- legged ticks can feed on mammals, birds, reptiles, and amphibians. Ticks

acquire Borrelia and other pathogens from infected hosts, and an interesting point is that female ticks do not transmit Borrelia to their offspring.13

Identifying ticks correctly is critical when discussing tick-borne disease, as diseases are often species-specific. For example, Ixodes ticks transmit Lyme disease, and Dermacentor transmits rickettsia. For this reason, experts advise people who are bitten to remove ticks properly, save them, and submit them to the local health department for identification.14

As researchers learn more about tick-borne diseases, they have found answers to many questions. They have determined that organisms that have complex life cycles, like ticks do, are more likely to be disease vectors. They have noted that infected ticks seem to be hardier than uninfected ticks. It also appears that pathogens modify tick behavior in remarkable ways:15

Infection with Borrelia and tick-borne encephalitis virus increases overall tick mobility considerably and improves phototaxis so that ticks can climb to higher questing heights; infected ticks can also walk faster and longer than uninfected ticks.

Borrelia and Anaplasma infection improve desiccation resistance in Ixodes ticks, allowing them to increase their fat reserves and synthesize heat shock proteins.

Anaplasma infections improve cold resistance in infected ticks.

Coinfection with Borrelia, Anaplasma, and B. microti lengthens life in infected ticks.

Babesia infection also helps ticks feed better (and become more engorged).

For these reasons, researchers describe infection as a win-win strategy for the pathogens and the ticks.

Ticks and Disease Transmission

Ticks infected with a pathogen may transmit disease to humans who are bitten by them. These tick-borne diseases include Rocky Mountain Spotted

Fever, anaplasmosis, babesiosis, ehrlichiosis, and tularemia. In addition, this section will discuss alpha-gal syndrome.

Rocky Mountain Spotted Fever and Rickettsiosis

Rocky Mountain Spotted Fever (RMSF) is discussed first because it was the first tick-borne disease identified.1 It is the most severe rickettsiosis in the United States. Howard Taylor Ricketts, an American pathologist, identified the Dermacentor andersoni wood tick as the vector for RMSF in 1906, and ultimately researchers found that other tick species, such as the American dog or wood tick (Dermacentor variabilis), were also vectors for RMSF.1

The pathogen family for RMSF, Rickettsiaceae, is named after Dr. Ricketts. Dr. Ricketts’ devotion to research was admirable but rather risky; he injected himself with suspected pathogens on several occasions. He was often so absorbed in his work that he became absent-minded. One anecdote about Ricketts describes his arrival at home to be told that his daughter had a temperature of 102°F. He responded that was normal but later realized he was preoccupied and incorrect. He admitted he had been thinking of guinea pigs, in which a temperature of 102°F would be normal.1

Five states (Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee) report more than 60% of RMSF cases, with cases peaking in the summer months (May through August).16 Of importance, RMSF occurs year- round in Arizona and Northern Mexico, which report unusually high incidences and case fatality rates, especially in children.17

Rocky Mountain Spotted Fever’s symptoms begin between three and 12 days after a tick bite.18 It generally begins with the abrupt onset of fever and headache that often prompt patients to seek care. Patients may develop gastrointestinal symptoms (nausea, vomiting, anorexia), acute abdominal pain that may be confused with appendicitis, myalgia, or rash that appears two to four days after the fever starts. Most of these symptoms are similar to those that develop in the remaining tick-borne diseases. One symptom that is different is edema around the eyes and on the back of the hands. More than

90% of patients develop small, flat, pink macules on the wrists, forearms, and ankles that spread to the trunk. Sometimes, the rash covers the palms and the soles of the feet.18

RMSF is rapidly progressive and immediate treatment is critical.18 Untreated, late illness develops, defined as symptoms after day 5. Untreated patients may develop petechiae (small spots of pinpoint bleeding under the skin) on day 5 or 6, and this development signals severe disease. Patients with severe disease may have altered mental status, coma, or cerebral edema; respiratory compromise (pulmonary edema, acute respiratory distress syndrome); necrosis from blood vessel damage that may lead to amputation; or multiorgan system damage. Risk factors for severe illness include delayed treatment, age younger than 10 (children account for 6% of cases but 11% of deaths), and glucose-6-phosphate dehydrogenase deficiency. After recovery from severe RMSF, patients often have permanent damage, including hearing loss, paralysis, or cognitive compromise. Permanent damage is caused by the acute illness, and RMSF does not become a chronic infection.18

Without early administration of doxycycline, RMSF can be fatal within days.18 Adults should receive 100 mg doxycycline every 12 hours, and children weighing less than 45 kg (100 lbs) should receive 2.2 mg/kg body weight given twice a day for at least three days after the fever subsides and clinical improvement is evident. All patients must be treated for at least five days and often longer.18

Pharmacy teams should note that starting in 1970, experts advised against using doxycycline in children younger than 8.19 The advice has changed. Using doxycycline for five to 10 days has been proven not to stain permanent teeth, cause enamel hypoplasia, or alter growth. Doxycycline is the first-line treatment for suspected RMSF in patients of all ages.19 Chloramphenicol is the alternative antibiotic for RMSF, but it is less effective. Patients with RMSF must not be treated with sulfa-containing drugs, as they worsen the clinical course and increase the risk of death.18

Anaplasmosis

A Gram-negative obligate intracellular bacterium that infects leukocytes causes anaplasmosis, formerly called human granulocytic ehrlichiosis.20 The Ixodes tick transmits its causative bacterium, A. phagocytophilum; similar to Lyme disease, the regional distribution of anaplasmosis is the Northeastern United States, upper Midwest, and northern California. Its prevalence peaks in the spring and summer.20 Recommended diagnostic tests include polymerase chain reaction (PCR) amplification on DNA extracted from whole blood specimens early in the illness (meaning in the first weeks). Note that a negative PCR does not rule out anaplasmosis. An indirect immunofluorescence antibody (IFA) assay is used to identify A. phagocytophilum, and patients must submit blood samples twice, two to four weeks apart.

Unlike Lyme disease, anaplasmosis is rarely associated with rash.20 Patients who contract anaplasmosis usually present with fever, malaise, myalgias, and severe headache within one to two weeks of a tick bite. They may also experience nausea, vomiting, and anorexia. Lab work may reveal various abnormalities, including leukopenia, thrombocytopenia, and elevated transaminases. If patients delay treatment, severe illness can develop, with possible respiratory failure, bleeding abnormalities, organ failure, and potentially, death. Older age and being immunocompromised increase the likelihood of severe illness.21

Experts recommend treatment with a 10-day course of doxycycline. In adults, the dosing is 100 mg every 12 hours. In children who weigh less than 45 kg (100 lbs), the dosing is 2.2 mg/kg given twice a day.21

POINT TO PONDER:

Which tick-borne diseases can and should be treated with doxycycline, and which would ideally be best referred to an infectious disease specialist?

Babesiosis

Babesiosis, a protozoan infection of the red blood cells, describes two human infections:22

Infection with Babesia microti. B. microti is transmitted to humans by Ixodes ticks with a disease distribution similar to Lyme disease.

Infection with B. divergens in immunocompromised human hosts, mainly in cattle-ranching regions during summer months.

In approximately one-half of cases, patients are co-infected with Lyme disease.23 Young, healthy patients with babesiosis are often asymptomatic. If symptoms develop, they are usually non-specific. Patients may experience a self-limited influenza-like low-grade febrile illness with anorexia, malaise, and lethargy. Complications can include hemolytic anemia, jaundice, and acute respiratory failure.22,23

Lab abnormalities include mild hemolytic anemia and thrombocytopenia.23 Treatment guidelines recommend using peripheral blood smear examination or PCR rather than antibody testing because Babesia antibodies can persist for a year or more after the infection has appeared to clear with or without treatment.22,23

Treatment is based on infection severity. Mild to moderate disease in immunocompetent patients is treated with azithromycin with a loading dose of 500 mg to 1000 mg followed by 250 to 1000 mg daily and atovaquone 750 mg twice daily for seven to 10 days. If babesiosis is severe, prescribers should employ quinine 650 mg three times daily and clindamycin 600 mg orally three times daily or 300 to 600 mg intravenously four times daily.24 Supportive care may include antipyretics. Patients who experience low or unstable blood pressure may need a vasopressor. In severe cases, blood or exchange transfusion, mechanical ventilation, or dialysis may be needed. If patients are highly immunocompromised, the guidelines recommend starting with regimens using the highest recommended doses or those recommended for hospitalized patients for six consecutive weeks or longer.24

Ehrlichiosis

Three bacteria cause ehrlichiosis in the United States: Ehrlichia chaffeensis, E. ewingii, or E. muris eauclairensis, with E. chaffeensis implicated most often.25 Clinicians are more likely to see cases in the southcentral and eastern U.S., where the lone star tick (Ambylomma americanum) is endemic. Cases linked to E. muris eauclairensis have only been reported in Minnesota and Wisconsin (as the name Eau-Clair-ensis suggests). The number of cases peaks in June and July every year.25

Signs and symptoms typically begin within five to 14 days after the bite of an infected tick.25 Ehrlichiosis manifests as an acute febrile illness with chills and rigors, but its presentation varies considerably among people and may include headache, malaise, myalgia, gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia), confusion, and rash. The rash is an interesting symptom, as it usually begins within five days of the first symptoms and occurs in up to 60% of children but only half as many adults. It usually appears on the body, but not the face, and may be maculopapular or petechial.25

Here, too, most cases are mild or moderate, but severe illness and death are possible.25 Severe illness is most likely to occur in patients who are very young, very old, or immunocompromised. Severe symptoms may include meningitis, meningoencephalitis, and other central nervous system involvement (which occurs in up to 20% of patients). Other complications may include acute respiratory distress syndrome, toxic shock-like or septic shock- like syndromes, renal or hepatic failure, or coagulopathies.25

No stand-alone guidelines exist for ehrlichiosis. Recommendations from the Centers for Disease Control and Prevention (CDC) are comprehensive and generally cover ehrlichiosis. Adults should receive 100 mg doxycycline every 12 hours, and children weighing less than 45 kg (100 lbs) should receive 2.2 mg/kg given twice a day for at least three days after the fever subsides and clinical improvement is evident. All patients must be treated for at least five days.25

Tularemia

Tularemia, caused by the bacterium Francisella tularensis, is also known as rabbit fever because rabbits, hares (which are larger and have longer ears than rabbits), and rodents are particularly susceptible and frequently die in large numbers during outbreaks. F. tularensis can also be spread by deer flies, contact with infected animals, drinking contaminated water or breathing contaminated dust. Its name is derived from Tulare County, California, where the disease was discovered in 1911.26 It is thankfully rare, with fewer than 300 cases reported annually.27

Symptoms of tularemia usually present one to 21 days after exposure, but most human infections develop in three to five days. Symptoms may include fever/chills, skin ulcers, and enlarged lymph nodes. Patients may also develop headache, malaise or fatigue, anorexia, chest discomfort, cough, sore throat, vomiting, diarrhea, and abdominal pain.27

Table 2 describes characteristic clinical variants of tularemia that develop based on the route of inoculation.27

Table 2

Clinical Variants of Tularemia and Their Presentations27

Patients will develop a fever ranging between moderate and very high intensity, and once it develops, the lab can isolate tularemia bacilli from blood cultures. Patients will experience facial and ocular reddening and inflammation that spreads to the lymph nodes, which enlarge and may exude pus if patients also have a high fever.27 Diagnosis follows isolation of F. tularensis from swabs or scrapings of ulcers, lymph node aspirates or biopsies, pharyngeal swabs, or respiratory specimens (e.g., pleural fluid). Laboratories need to know if F. tularensis is suspected so they can incubate cultures for extended periods; F. tularensis grows slowly. Clinicians can also monitor seroconversion from negative to positive IgM and/or IgG antibodies in two serum samples, one within the first week of acute onset and the second serum sample two to three weeks later.27

In this tick-borne infection, patients will need immediate treatment with more than just doxycycline, and in this instance, clinicians need to consider consultation with an infectious disease specialist seriously.27 Table 3 describes current treatment recommendations. Gentamicin is preferred for the treatment of severe tularemia, and infectious disease specialists may recommend combination therapy. Gentamycin and ciprofloxacin are used off- label in this indication.27

Table 3

Recommended Treatments for Tularemia27

POINT TO PONDER:

Which patients are most likely to develop α-gal Syndrome, and what should pharmacy staff monitor?

Alpha(α)-gal Syndrome

A CDC report showed that between 2010 and 2022, clinicians reported more than 110,000 suspected cases of α-gal syndrome. However, α-gal syndrome is not a nationally notifiable disease, so the CDC indicates many cases may be unreported or undiagnosed. The CDC has made a public push to heighten awareness of this tick-borne, serious, potentially life-threatening allergic condition. α-gal syndrome is also called α-gal allergy, red meat allergy, or tick bite meat allergy. α-gal syndrome is not an infection but a serious allergy that develops after a tick bite in some people. Symptoms occur after consumption of red meat or exposure to products containing α-gal.

Alpha-gal (galactose-α-1,3-galactose) is a sugar molecule that is present in non-primate mammals but not birds, fish, or humans. It is present in red meats and products made from mammals like gelatin, cow’s milk, and milk products. α-gal syndrome has been linked to bites from lone star ticks in the U.S. The CDC is unsure if other ticks can cause α-gal syndrome, but several tick species have been proven to cause α-gal syndrome in other countries.

In addition to the risk factors associated with tick bites, a small study found certain people are more likely to develop α-gal syndrome. Predisposing factors included28

a history of childhood allergies

allergies to foods other than red meat

A propensity to have cutaneous reactions to insect bites, and

sIgE antibodies to many allergens

family members (parents, siblings, and children) with food allergies and allergies to insect bites.

The researchers indicated that patients with α-gal syndrome were roughly eight times as likely to report related family members with α-gal syndrome. A or O blood types seem to increase risk, while risk in people with

AB or B blood types seems to be lower. These findings suggest a genetic component for susceptibility.28

Alpha-gal allergic reactions range from mild to life-threatening anaphylaxis.29 Affected patients will experience symptoms two to six hours after consuming meat or other mammalian products. Symptoms may include hives; swelling of the lips, tongue, throat, or eyelids; cough; difficulty breathing; wheezing; heartburn; nausea or vomiting; abdominal pain; diarrhea; or decreased blood pressure. Diagnosis requires blood testing to identify the antibody against the α-gal sugar molecule.29

If patients have mild α-gal symptoms, antihistamines can help. Those who experience more severe reactions will require intramuscular epinephrine and may need supportive care in the emergency department.30

Patients with α-gal syndrome must abstain from mammalian meat (e.g., beef, pork, or lamb) and should avoid future tick bites. Some affected patients may need to stop consuming mammalian-based products (such as cow’s milk, cheese, or gelatin). The CDC maintains a list of α-gal-containing products here: https://www.cdc.gov/ticks/alpha-gal/products.html.31 Clinicians should avoid prescribing α-gal-containing medications (e.g., heparin, snake antivenom, certain cancer medications [such as cetuximab]), and mammal- based organ replacements (such as heart valves).

A Word About Pregnancy

Clinicians should approach diagnosis and laboratory testing for tick- borne disease in pregnant women following current recommendations and guidelines for other adult patients. As noted above, prescribers avoided doxycycline in pregnancy and children younger than eight because of concerns about adverse effects (teeth staining and delayed bone growth). Systematic review indicates these concerns are unwarranted.32 However, if a pregnant woman cannot take doxycycline, clinicians may consider using oral amoxicillin 500 mg three times daily or oral cefuroxime axetil 500 mg twice daily for 14 to 21 days. Azithromycin 500 mg is an alternative, but less evidence supports

its use. The safest approach to treating pregnant women in whom doxycycline is contraindicated is consultation with an infectious disease specialist.32

In the Pharmacy

Dealing with tick-borne disease is complicated, and patients often cannot remember or do not notice a tick bite—a situation that occurs in 30% to 50% of individuals.33 Ixodes ticks are about the size of a sesame seed, while common dog ticks are 5 mm or larger (the size of a pencil top eraser). Larval and nymphal ticks (which are often implicated in tick bites) are a few millimeters in diameter; adult ticks are larger. Tick bites are easy to miss. This is yet another reason misdiagnosing or delayed diagnosis is common.34

Pharmacists and pharmacy technicians will note that in almost all tick- borne diseases, doxycycline is the drug of choice. Healthcare providers should be cautious when exploring treatments other than doxycycline for most tick- borne infections, and consulting an infectious disease specialist is a smart move. A key point to remember is that package inserts still advise against using doxycycline during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years).35 This information is now outdated, and doxycycline is considered a front-line short-term treatment for tick-borne disease in children and pregnant women.19 Doxycycline can cause photosensitivity, and patients need to limit sun exposure and use sunscreen while on it. Most common adverse reactions include anorexia, nausea, vomiting, diarrhea, rash, photosensitivity, urticaria, and hemolytic anemia.35 Pharmacists need to screen for drug interactions with doxycycline. Prescribers may need to adjust anticoagulant therapy downward.35 Doxycycline should not be given concurrently with penicillin. Concurrent antacids containing aluminum, calcium, magnesium, bismuth subsalicylate, and iron-containing preparations will impair doxycycline’s absorption. Some evidence suggests concurrent use of tetracyclines decreases oral contraceptives’ effectiveness, and patients should use a backup measure to prevent pregnancy. Barbiturates, carbamazepine, and phenytoin decrease doxycycline’s half-life. Patients should also take doxycycline on an empty stomach.35

Encouraging and monitoring adherence is critical. Applying appropriate auxiliary labels and counseling the patient to take the medication precisely as prescribed can improve outcomes. Pharmacy teams should suggest using adherence tools like cell phone alarms or medication boxes to ensure complete adherence to the entire course of treatment.

One point is important to make and repeat: contracting a tick-borne disease does not give patients immunity in the future, so they need to take steps to prevent future bites.36 Prevention needs to be emphasized repeatedly, as does prompt tick removal. Table 4 provides links to materials that can help patients prevent tick exposure, use appropriate tools and techniques for tick removal, identify a tick by species, and understand tick-borne disease.

Knowing which effective insecticides are in stock in the pharmacy is also important. The CDC recommends treating clothing and gear with products containing 0.5% permethrin. The Environmental Protection Agency (EPA) produces and maintains a list of registered insect repellents effective against ticks; the list includes repellents containing DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE, which must not be used on children younger than 3), para-menthane-diol (PMD), or 2-undecanone. The EPA also provides a search tool that helps individuals find appropriate products (see https://www.epa.gov/insect-repellents/find-repellent-right-you). On this site, patients indicate how much time they will be outside and the organism against which they want protection, and the search engine does the rest.

Table 4

Patient Resources for Tick Bite Prevention and Detection

Individuals diagnosed with α-gal syndrome are typically prescribed an epinephrine auto-injector to use if they develop a severe allergic reaction. Pharmacy technicians can be of great help when that is the case and remind patients to note the expiration date so they can replace the medication. They also need to remind parents to examine local school policy and make sure the school identifies employees who can administer the injection in the school, and also on field trips. In addition, pharmacy technicians can remind patients and parents that epinephrine is weight based, and once a child weighs 30 kg (66 lbs), the dose needs to increase from 0.15 mg to 0.3 mg.37

Pointing out that the CDC maintains a site that lists products containing α-gal like gelatin, glycerin, magnesium stearate, and bovine extracts, provides a tool to manage the condition.

Finally, pharmacists and technicians need to remember that all tick- borne diseases are zoonotic diseases. Zoonotic diseases are diseases that are transmitted from animals to humans, and that means that people who own companion animals, especially dogs, need to be vigilant about ticks.38 In the United States, dog owners are notorious for skimping on flea and tick preventive treatments or using natural remedies when medications are much more effective. In a typical year, a majority of owners only purchase seven months of preventive medications; their dogs are unprotected for five months of the year.38 Owners need to be certain that their dogs are on an effective tick preventive year-round (some owners mistakenly think they can stop the preventive in the colder months; that is a bad idea).38

Summary

As noted in our introduction, tick-borne disease is on the uptick. Researchers are learning more about the various types of tick-borne diseases, the ticks that are most likely to cause these diseases, and the geographic locations that are most affected. As noted in Table 1, a total of 12 tick-borne diseases appear in humans. Some of them have no current treatments. It is likely that researchers will identify additional tick-borne diseases in the future, and they may find effective treatments for the four diseases discussed above and the alpha-gal syndrome. In the pharmacy, pharmacists and pharmacy technicians will do well to have a high index of suspicion for these diseases and be able to differentiate between the various types.

Course Test

Which of the following tick-borne diseases would be considered a serious rickettsial disease?

Anaplasmosis

Babesiosis

Ehrlichiosis

Rocky Mountain spotted fever

Which of the following has a geographic distribution similar to Lyme disease?

Anaplasmosis

Babesiosis

Ehrlichiosis

Rocky Mountain spotted fever

A patient is diagnosed with a tick-borne disease and is coinfected with Lyme disease. The diagnostician indicates that in approximately 1/2 of cases, patients diagnosed with this tick- borne disease also have Lyme disease. What diagnosis is it?

Anaplasmosis

Babesiosis

Ehrlichiosis

Rocky Mountain spotted fever

A patient reports that she removed an engorged tick from her back six weeks ago. She has struggled with nausea and anorexia for the last week. Her favorite meal is a Big Mac with French fries, but even the thought of it makes her want to throw up. Her tests for Lyme disease were negative. She has type O blood and a history of allergies. What might her diagnosis be?

Anxiety

Hypochondria

Pregnancy

Alpha-gal (α-gal) syndrome

Which of the following medications might be considered to treat tularemia in a hospital setting?

Cephalexin, doxycycline, or griseofulvin

Ciprofloxacin, doxycycline, or gentamicin

Ciprofloxacin, oxacillin, or gentamicin

Griseofulvin, infliximab, or losartan

Which of the following medications would be considered supportive care for a patient who has babesiosis?

Acetaminophen plus a vasopressor

An antiemetic plus an antihypertensive

Hydrocortisone cream plus an antihistamine

Intravenous fluids with vitamins

What do the guidelines recommend when treating patients who are highly immunocompromised?

Starting with a low dose and increasing the antibiotic gradually

Starting with regimens using the highest recommended doses

Using a medication other than doxycycline for tick-borne diseases

Discontinue any corticosteroids or meds for the immune condition

A patient comes to the pharmacy to pick up medication for a tickborne disease. He indicates that his dog carries ticks into the house all the time. What should you tell him?

Be sure to treat your dog with a tick preventive year-round; dogs can pick up ticks any day of the year.

Treat your dog with a tick preventive between April and October. That's when ticks are most likely to be active.

Would you like to speak to the pharmacist about tick prevention for your dog?

You should consider using a natural remedy for ticks, like apple cider vinegar or salt.

A patient comes to the pharmacy and says that she has recently been diagnosed with α-gal syndrome. In your discussion with her, what would be an appropriate statement?

Let me connect you to the pharmacist so he can call your provider and get you started on doxycycline.

The Environmental Protection Agency has a website that lists products that contain α-gal.

Once you complete a round of treatment, you should be able to eat meat again.

The CDC has an excellent website that has patient education on alpha-gal syndrome and its management.

A parent indicates that she has a prescription for her 7-year-old for doxycycline. She did some Internet research and read the package insert. She says that she doesn't think she should give doxycycline to her child because it will stain the child's teeth. What is the best response?

Recent research indicates that short courses of doxycycline are unlikely to stay in a child's teeth, and this is the preferred drug for tick-borne infections.

I see the same thing that you do in the package insert, and I need to ask the pharmacists to call the prescriber and have this prescription changed to ciprofloxacin or gentamicin.

It is dangerous to rely on information from the Internet but in this case, I think you are correct. Most kids recover from tick-borne diseases without treatment, so you can skip the doxycycline.

The staining usually happens immediately, and the new tooth- whitening products will take care of any staining. Would you like me to help you find them so you can select one?

References

Weiss E, Strauss BS. The Life and Career of Howard Taylor Ricketts.

RID. 1991;13 (November-December):1241-1242.

Rosenberg R, Lindsey NP, Fischer M, et al. Vital Signs: trends in reported vectorborne disease cases - United States and territories, 2004-2016. MMWR Morb Mortal Wkly Rep. 2018;67(17):496-501.

Centers for Disease Control and Prevention. Diseases Transmitted by Ticks. CDC. Updated September 11, 2023. https://www.cdc.gov/ticks/diseases/index.html. Accessed February 7, 2024.

Krause PJ, McKay K, Thompson CA, et al.. Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin Infect Dis. 2002;34:1184-1191. 10.1086/339813

Rodino KG, Theel ES, Pritt BS. Tick-Borne Diseases in the United States.

Clin Chem. 2020;66(4):537-548. doi:10.1093/clinchem/hvaa040

Krause PJ, McKay K, Thompson CA, et al. Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin Infect Dis. 2002;34(9):1184-1191. doi:10.1086/339813

Ostfeld RS. Ecology of Lyme Disease. IN: Fundamentals of Ecosystem Science, Weathers KC, Strayer DL, Likens GE, eds. Academic Press. file:///C:/Users/Jeannette/Downloads/FundamentalsofEcosystemScienc e_ByWeathersetal_2012_Final.pdf. Accessed February 10, 2024.

Opossums - killers of ticks. Cary Institute. April 18, 2014. https://www.caryinstitute.org/news-insights/media- coverage/opossums-killers-ticks. Accessed February 10, 2024.

Aristizabal-Henao JJ, Brown HJ, Griffin EK, et al. Ticks as novel sentinels to monitor environmental levels of per- and polyfluoroalkyl substances (PFAS). Environ Sci Process Impacts. 2021;23(9):1301-1307. Published 2021 Sep 23. doi:10.1039/d1em00209k

Bratton RL, Whiteside JW, Hovan MJ, et al. Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008;83(5):566-571.

Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010;30:311328.

Wright WF, Riedel DJ, Talwani R, Gilliam BL. Diagnosis and management of Lyme disease. Am Fam Physician. 2012;85:1086-1093.

Lyme Disease. Transmission. Centers for Disease Control and Prevention. Updated January 20, 2023. https://www.cdc.gov/lyme/transmission/index.html. Accessed March 11, 2024.

Lantos PM, Rumbaugh J, Bockenstedt LK, et al. 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. Clin Infect Dis. 2021;72(1):1-8. doi:10.1093/cid/ciab049

Benelli G. Pathogens Manipulating Tick Behavior-Through a Glass, Darkly. Pathogens. 2020;9(8):664. Published 2020 Aug 17. doi:10.3390/pathogens9080664

Adjemian JZ, Krebs J, Mandel E, McQuiston J. Spatial clustering by disease severity among reported Rocky Mountain spotted fever cases in the United States, 2001-2005. Am J Trop Med Hyg. 2009;80(1):72-77.

Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever. Transmission and Epidemiology. CDC. Updated October 26, 2018. https://www.cdc.gov/rmsf/healthcare-providers/transmission-

epidemiology.html. Accessed February 7, 2024.

Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever. Signs and Symptoms. CDC. Updated February 19, 2019. https://www.cdc.gov/rmsf/healthcare-providers/signs-symptoms.html. Accessed February 7, 2024.

Centers for Disease Control and Prevention. Research on doxycycline and tooth staining. CDC. Updated February 19, 2019. https://www.cdc.gov/rmsf/doxycycline/index.html. Accessed February 7, 2024.

Centers for Disease Control and Prevention. Anaplasmosis. Transmission and Epidemiology. CDC. Updated January 11, 2019. https://www.cdc.gov/anaplasmosis/healthcare-providers/transmission- epidemiology.html. Accessed February 7, 2024.

Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the infectious diseases Society of America. Clin Infect Dis. 2006;43:1089–

134. 10.1086/508667

Centers for Disease Control and Prevention. Parasites – Babesiosis, Resources for Health Professionals. CDC. Updated June 16, 2023. https://www.cdc.gov/parasites/babesiosis/health_professionals/index.ht ml. Accessed February 7, 2024.

Mareedu N, Schotthoefer AM, Tompkins J, Hall MC, Fritsche TR, Frost HM. Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis. Am J Trop Med Hyg. 2017;97(4):1218-1225. doi:10.4269/ajtmh.17-0146

Krause PJ, Auwaerter PG, Bannuru RR, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. Clin Infect Dis. 2021;72(2):185-189. doi:10.1093/cid/ciab050

Centers for Disease Control and Prevention. Ehrlichiosis. Information for Healthcare providers. CDC. Updated June 16, 2023.

https://www.cdc.gov/ehrlichiosis/healthcare-providers/index.html. Accessed February 7, 2024.

Hirschmann JV. From Squirrels to Biological Weapons: The Early History of Tularemia. Am J Med Sci. 2018;356(4):319-328. doi:10.1016/j.amjms.2018.06.006

Centers for Disease Control and Prevention. Tularemia. For Clinicians. CDC. Updated July 5, 2022. https://www.cdc.gov/tularemia/clinicians/index.html. Accessed February 7, 2024.

Taylor ML, Kersh GJ, Salzer JS, et al. Intrinsic risk factors for alpha-gal syndrome in a case-control study, 2019-2020. Ann Allergy Asthma Immunol. Published online February 8, 2024. doi:10.1016/j.anai.2024.01.029

Mollah F, Zacharek MA, Benjamin MR. What Is Alpha-Gal Syndrome?. JAMA. 2024;331(1):86. doi:10.1001/jama.2023.23097

Iglesia EGA, Kwan M, Virkud YV, Iweala OI. Management of Food Allergies and Food-Related Anaphylaxis. JAMA. 2024;331(6):510-521. doi:10.1001/jama.2023.26857

Products That May Contain Alpha-gal. Centers for Disease Control and Prevention. Updated July 27, 2023. https://www.cdc.gov/ticks/alpha-

gal/products.html. Accessed February 7, 2024.

Smith GN, Moore KM, Hatchette TF, Nicholson J, Bowie W, Langley JM. Committee Opinion No. 399: Management of Tick Bites and Lyme Disease During Pregnancy. J Obstet Gynaecol Can. 2020;42(5):644- 653. doi:10.1016/j.jogc.2020.01.001

Aucott J, Morrison C, Munoz B, et al. Diagnostic challenges of early Lyme disease: lessons from a community case series. BMC Infect Dis 2009;9:79.

Girschick HJ, Morbach H, Tappe D. Treatment of Lyme borreliosis. Arthritis Res Ther. 2009;11(6):25835. Doxycycline

(prescribing information). Mylan Pharmaceuticals, Inc. April 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/90431Ori g1s010lbl.pdf. Accessed February 7, 2024.

Cross R, Ling C, Day NP, McGready R, Paris DH. Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation?. Expert Opin Drug Saf. 2016;15(3):367-382. doi:10.1517/14740338.2016.1133584

Epinephrine auto-injector (prescribing information). January 2010. Greenstone, LLC. 020800s020lbl.pdf (fda.gov). Accessed February 7, 2024.

Shapiro ED. Repeat or persistent Lyme disease: persistence, recrudescence or reinfection with Borrelia Burgdorferi?. F1000Prime Rep. 2015;7:11. doi:10.12703/P7-11

Lavan R, Armstrong R, Lipworth K, Normile D, Newbury H. Flea and tick treatment satisfaction, preference, and adherence of dog owners in the United States, United Kingdom, and Australia who treated their dog with fluralaner. Open Vet J. 2020;10(2):135-143. doi:10.4314/ovj.v10i2.3

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