Evaluation of a tick bite for possible Lyme disease

INTRODUCTION — Lyme disease is the most common tickborne disease in the United States, Canada, and Europe. It is a spirochetal infection caused by species in the spirochete family Borreliaceae. The taxonomy of these spirochetes is undergoing revision, and the genus name may be represented as either Borrelia or Borreliella. In either case, the abbreviation for the genus is "B" and stands for both terminologies in the discussion below.

Borrelia burgdorferi in the United States and primarily B. afzelii and B. garinii in Europe and Asia are transmitted by the bite of infected Ixodes ricinus complex ticks. Lyme disease can involve the skin, joints, nervous system, and heart. In the United States, Ixodes ticks can also transmit human granulocytic anaplasmosis and babesiosis. In Europe, they can also transmit tickborne encephalitis virus, and in the US, they may transmit a closely related virus called the Powassan encephalitis virus (also called the deer-tick virus).

Ticks have three stages in their life cycle: larva, nymph, and adult. Lyme disease is most commonly transmitted by nymphal ticks, which are typically most active during the late spring and early summer in temperate regions. Adult ticks can also transmit Lyme disease, but this occurs less commonly because adult ticks are less likely to bite humans and because they are larger and thus more likely to be detected and removed promptly. Adult ticks are most active on warm days in the fall.

Individuals at highest risk for Lyme disease are those who live in an endemic region and have occupational (eg, forestry and telephone line workers) or recreational (eg, hunting, camping, hiking, gardening, children playing in wooded areas) exposure to ticks (figure 1). However, in highly endemic areas, people may be at risk even in their yards, particularly where grassy areas and woodlands meet.

The factors affecting transmission of Lyme disease, methods for tick removal, and indications for antibiotic prophylaxis following a tick bite are reviewed here. The epidemiology, microbiology, prevention, diagnosis, clinical manifestations, and treatment of Lyme disease are discussed separately. (See "Epidemiology of Lyme disease" and "Microbiology of Lyme disease" and "Prevention of Lyme disease" and "Diagnosis of Lyme disease" and "Clinical manifestations of Lyme disease in adults" and "Treatment of Lyme disease".)

FACTORS AFFECTING TRANSMISSION — Asking the following questions can aid in the risk assessment for Lyme disease following a tick bite:

●Was the tick a member of the Ixodes species?

●Was the tick a larval, nymphal, or adult tick?

●Was the tick attached?

●How long was the tick attached?

●Was the tick engorged?

The importance of these factors is discussed below.

Tick size and appearance — Tick size and appearance can be helpful clues for determining the risk of disease transmission, but the validity of this information is highly dependent upon the expertise of the person viewing the tick. Patients sometimes confuse tick bites with bites by other types of arthropods. As an example, in one study 6 percent of specimens submitted by clinicians for tick identification were actually arthropods (most commonly beetles and lice) rather than ticks [1]. (See "Insect and other arthropod bites".)

Nymphal Ixodes ticks are typically tiny and round (about the size of a poppy seed) before feeding. Nymphal stages of the American dog tick, Dermacentor variabilis, rarely bite humans, and nymphal stages of the lone star tick, Amblyomma americanum, are larger in comparison to Ixodes ticks (picture 1 and figure 2). Amblyomma ticks are found primarily in southern and mid-Atlantic states (figure 3). The 10 states with the highest incidence of Lyme disease include Maryland, Delaware, Pennsylvania, New Jersey, New York, Connecticut, Rhode Island, and Massachusetts along the Atlantic seaboard, as well as Minnesota and Wisconsin in the upper Midwest (figure 1 and table 1) [2].

Adult Ixodes scapularis are larger than nymphal forms. Unengorged adults are approximately 3 mm in length. Female Ixodes ticks are orange-reddish, with a dark brown oval-shaped structure called a scutum covering the superior portion of the dorsal surface (picture 2); in contrast, the dorsal surface of male Ixodes ticks is uniformly brown since the entire surface is covered by a large scutum (figure 2). Adult female A. americanum ticks have a solitary white spot on their back (the "lone star") (picture 3). Adult male A. americanum ticks have an interconnected ring of white markings (figure 2). Dermacentor and Amblyomma ticks are not vectors of Lyme disease, although the former can transmit Rocky Mountain spotted fever and the latter is the vector of human monocytic ehrlichiosis. Amblyomma ticks have also been implicated in STARI (Southern tick-associated rash illness), which causes an expanding skin lesion similar to erythema migrans (EM). Although an infectious agent is thought to be the cause of STARI, none has yet been conclusively identified [3,4]. While the skin lesion of STARI is similar to the EM rash of Lyme disease, STARI is not known to have the later manifestations associated with Lyme disease. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever" and "Human ehrlichiosis and anaplasmosis" and "Southern tick-associated rash illness (STARI)".)

In the United States, the Centers for Disease Control and Prevention (CDC) website provides information on where different types ticks are found.

Tick attachment — Ticks that are feeding are firmly attached to the skin. A tiny, round tick that is walking on the skin surface or that is easily removed has not yet started the feeding process and is thus not capable of transmitting Lyme disease.

The duration of tick attachment is important in assessing the risk of transmission of Lyme disease. B. burgdorferi are rarely transmitted within the first 48 hours of tick attachment [5-8]. As examples:

●A study of Lyme disease prevention found that among subjects bitten by nymphal ticks in whom the duration of attachment could be estimated, the risk of Lyme disease was 25 percent if the tick had fed for 72 hours compared with 0 percent if the tick had fed for a shorter period [5]. A separate study found that the incidence of Lyme disease was significantly higher when the duration of attachment was at least 72 hours: 3 of 15 such patients (20 percent) developed Lyme disease, compared with 1 of 94 (1 percent) in whom the tick was attached for less than 72 hours [8].

●In another study, the risk of Lyme disease transmission from a firmly attached but unengorged tick was only 1 percent in a trial that was performed in a Lyme-endemic area in which approximately 15 percent of ticks were infected with B. burgdorferi [9].

As feeding ticks become engorged with blood, they release their saliva into the bite wound. However, animal studies suggest that spirochetes are not found in the tick’s saliva until approximately 48 hours after it starts to feed. One study, for example, found that spirochetes are restricted to the lumen of the tick gut in unfed Ixodes ticks [10]. When the nymphal ticks fed on mice, the number of spirochetes in the gut subsequently increased. It was only after 48 hours of feeding that the spirochetes disseminated to the salivary glands. Although similar studies have not been done in humans, it is anticipated that the behavior of the organism will be similar.

The 48-hour period required for B. burgdorferi to migrate from the midgut to the salivary glands of the Ixodes tick contrasts with the much shorter time required for ticks of the same species to transmit the organisms that cause human granulocytic anaplasmosis (HGA, previously called human granulocyte ehrlichiosis; Anaplasma phagocytophilum) and babesiosis (Babesia microti). Babesia and Anaplasma spp are present in the tick's salivary glands before feeding has begun. Thus, the duration of tick attachment is less important for the risk assessment of transmission of these diseases. The transmission times for other less common tick borne illnesses (eg, Borrelia miyamotoi, Powassan virus) are not well understood. More detailed discussions of transmission are presented in separate topic reviews. (See "Epidemiology of Lyme disease", section on 'Transmission to humans' and "Human ehrlichiosis and anaplasmosis" and "Babesiosis: Microbiology, epidemiology, and pathogenesis" and "Arthropod-borne encephalitides", section on 'Powassan virus' and "Borrelia miyamotoi infection".)

Although it is often difficult to determine how long a tick has been attached, it may be helpful if the patient can remember a situation in which he or she could have acquired a tick bite (eg, a walk through the woods).

Ticks detach and fall off after becoming engorged from a blood meal. Engorged ticks are larger and have a globular shape (picture 1). Thus, if a patient reports finding an engorged tick (on their body or in their home), the risk of disease transmission is probably higher.

MANAGEMENT — Prompt removal of attached ticks is the first step to prevent transmission of Lyme disease after a tick bite [5-8,11,12]. Following tick removal, some patients may benefit from antimicrobial prophylaxis. These issues are discussed in detail below.

Technique for tick removal

To minimize retention of residual tick parts in the skin, various tick removal techniques have been studied. No studies have evaluated whether tick removal techniques affect the transmission of B. burgdorferi from ticks to humans [11,12].

Proper technique for removal of an attached tick includes the following steps (figure 4) [11,12]:

●Use fine-tipped tweezers (or small forceps) to grasp the tick as close to the skin surface as possible. The tweezers should grasp the head of the tick and avoid compressing the tick’s body. In the absence of tweezers or forceps, remove by hand using paper or cloth to protect the fingers during tick extraction.

●Pull straight up gently but firmly, using steady pressure.

•Do not squeeze, crush, or puncture the body of the tick because its fluids may contain infectious agents.

●Do not jerk or twist the tick since this may cause mouth-parts to break off and remain in the skin.

•If the tick’s mouth-parts remain in the skin, we suggest waiting for the parts to fall out spontaneously; digging them out may increase the risk of soft tissue infection [11].

●After removing the tick, disinfect the bite site and cleanse your hands with alcohol or soap and water.

●After tick removal, the bitten person (or caregivers) should observe the bite site for the development of erythema migrans (EM) for 30 days. Components of tick saliva can cause transient erythema that should not be confused with EM.

Techniques that are not recommended include the application of petroleum jelly, fingernail polish, isopropyl alcohol, or a hot match. Unlike the use of tweezers, these techniques have been found to increase the likelihood of tick mouth-parts being left in host skin [13].

In some countries, such as Australia, freezing ticks before removal is advocated because the local ticks (Ixodes holocyclus) cause toxin-mediated paralysis, and there is concern that removal without killing first may increase toxin release. However, in most other settings this is not necessary [11].

Antimicrobial prophylaxis — Antimicrobial prophylaxis with doxycycline after a tick bite is reasonable for certain patients. However, this approach should not replace other preventive measures, which are discussed in detail elsewhere. (See "Prevention of Lyme disease".)

Approach to prophylaxis

●Indications – Antibiotic prophylaxis is indicated for nonpregnant adults and children who meet all of the following criteria [11]:

•Attached tick is identified as an adult or nymphal I. scapularis tick (deer tick). (See 'Tick size and appearance' above.)

•Tick is estimated to have been attached for ≥36 hours based on degree of engorgement or time of exposure.

•Prophylaxis is begun within 72 hours of tick removal.

The bite occurs in a highly endemic area. In the United States, this information can be found on the Centers for Disease Control and Prevention (CDC) website.

•Doxycycline is not contraindicated. (See "Tetracyclines", section on 'Special populations' and "Tetracyclines", section on 'Adverse reactions'.)

In pregnant patients, a single dose of doxycycline is very unlikely to cause harm to the fetus or mother, and there is no reason to believe the benefit of doxycycline prophylaxis would be any less during pregnancy. Although older tetracyclines are contraindicated in pregnancy because of the risk of hepatotoxicity in the mother and adverse effects on fetal bone and teeth, the avidity of doxycycline for calcium is low and it is felt to be safe for short course use in pregnant women and young children, particularly when there are no other options for treatment [14]. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Antibiotics' and 'Efficacy and rationale' below.)

●Antimicrobial regimen – For patients who meet criteria for prophylaxis, the recommended dose of doxycycline is 200 mg for adults and 4.4 mg/kg up to a maximum dose of 200 mg in children, given as a single dose. Guidelines state that, in areas of high risk, a single prophylactic dose of doxycycline can be used in children of any age to reduce the risk of acquiring Lyme disease after the bite of an infected I. scapularis tick [11,15]. However, in children, the efficacy of this approach and the appropriate regimen have not been established, since doxycycline prophylaxis has not been studied in children <12 years of age and recommendations are extrapolated largely from the adult experience. (See 'Efficacy and rationale' below.)

If the patient meets criteria for prophylaxis, but cannot take doxycycline (eg, known adverse reactions or contraindication), we agree with guidelines and generally do not administer an alternate antibiotic or treatment regimen [11]. There are no data to support the efficacy of a short course of another antibiotic; longer courses of antibiotics may lead to adverse effects; standard antibiotic treatment is highly effective if Lyme disease actually occurs; and the risk of developing a serious complication of Lyme disease after a recognized tick bite is extremely low.

●Patients who do not take prophylaxis – For patients who do not take prophylaxis (eg, they do not meet criteria, they cannot take doxycycline, they choose not to take prophylaxis), an acceptable alternative is observation of the tick bite site and treatment for Lyme disease if an EM rash develops. This approach is reasonable since most patients who are infected with B. burgdorferi develop EM, and the outcomes with early therapy are excellent [16,17]. (See "Treatment of Lyme disease".)

It should also be remembered that Lyme disease less often results from a recognized tick bite, since removal of the tick within two to three days of attachment usually prevents transmission of B. burgdorferi. More commonly, Lyme disease is transmitted by an unrecognized tick that feeds to repletion (about four to five days) and then falls off without the person knowing that he or she has been bitten.

Efficacy and rationale — Although the treatment of EM results in complete resolution of symptoms in at least 90 percent of patients [16,17], some clinicians and patients have expressed concerns that treating only patients who show signs of illness will leave a subset of individuals with untreated subclinical disease. It has been hypothesized that such patients may then progress to more serious and difficult-to-treat sequelae. If this were true, then pre-emptive therapy might be beneficial. To this end, several studies have investigated the efficacy of giving antibiotics at the time of a tick bite to prevent Lyme disease.

●Efficacy of doxycycline – Antibiotic prophylaxis with a single dose of doxycycline has been found to be effective in patients who meet a specified set of criteria. A randomized, double-blind trial involving 482 patients ≥12 years of age residing in an endemic area from whom I. scapularis ticks had been removed within the previous 72 hours demonstrated that doxycycline (200 mg orally as a single dose) was effective in preventing Lyme disease (0.4 versus 3.2 percent for placebo) [5]. Only engorged nymphal ticks transmitted the disease. However, doxycycline caused more adverse effects than placebo (30 versus 11 percent). The most common side effects of doxycycline were nausea and vomiting.

The efficacy of doxycycline prophylaxis was 87 percent in this trial, but the 95 percent confidence interval was wide (25 to 98 percent) because there were few cases of Lyme disease [5]. Data from this trial suggest that it would be necessary to give doxycycline to approximately 40 people to prevent one case of Lyme disease; 125 people would need to be treated if the efficacy was at the lower end of the calculated confidence interval. These estimates were based on exposure to ticks in an area with a relatively high incidence of Lyme disease (Westchester County, New York, where the incidence of Lyme disease was 0.5 to 1.0 reported cases per 1000 persons per at the time of the study). In most areas of the United States, the risk of Lyme disease is much lower, and thus the benefit of prophylactic doxycycline would be correspondingly much lower as well.

A more recent trial evaluated doxycycline prophylaxis after bites from the Ixodes ricinus tick in Europe [18]. The trial found that doxycycline (200 mg orally as a single dose) was effective at preventing Lyme disease (0.96 versus 2.9 percent for placebo), and the estimated number needed to treat to prevent one case was 51.

A cost-benefit analysis of doxycycline prophylaxis for Lyme disease after a tick bite concluded that prophylaxis would be warranted if the incidence of Lyme disease following a tick bite was 3.6 percent [19]. In the doxycycline prophylaxis trial described above, the risk of Lyme disease in patients bitten by nymphal ticks was higher if the tick was at least partially engorged (10 percent) than if it appeared flat (0 percent) [5]. Thus, antibiotic prophylaxis may be cost-effective after removal of an engorged Ixodes tick in Lyme-endemic regions.

●Efficacy with other agents – Amoxicillin has been evaluated for prophylaxis after a tick bite, but the trials were underpowered [9,20,21]. Meta-analyses of these trials failed to demonstrate a beneficial effect against the subsequent development of Lyme disease [22,23].

Topical azithromycin was shown in a randomized placebo-controlled trial in Europe to be ineffective for reducing Lyme seroconversion [24].

●Risk of resistance – A potential concern with antibiotic prophylaxis is, if it is not successful in eradicating the bacteria, whether there will be changes in the course of infection that will make it difficult to diagnose Lyme disease or make it more resistant to subsequent treatment. There is currently no evidence to support this concern.

Serologic testing — At the time of a tick bite, serologic testing should not be obtained to establish a new diagnosis of B. burgdorferi infection because antibodies to the spirochete would not yet have appeared.

Following the onset of EM:

●Immune globulin (Ig) M antibodies to B. burgdorferi typically appear within one to two weeks.

●IgG antibodies to B. burgdorferi typically appear within one to six weeks, depending upon the type of test that is used (eg, C6 versus Western blot).

In addition, we typically do not perform routine follow-up testing four to six weeks after the bite for asymptomatic patients, since one would have to test many patients to find an asymptomatic seroconverter and the benefit of antimicrobial therapy in asymptomatic patients is unclear. (See "Treatment of Lyme disease", section on 'Asymptomatic seropositive individuals'.)

A more detailed discussion on the use of serologic testing for the diagnosis of Lyme disease is found elsewhere. (See "Diagnosis of Lyme disease".)

Testing ticks — In most cases we do not send ticks for species identification if a tick is removed and available for testing. Although some clinicians find it helpful, as this information can be used to counsel patients on the potential risk of Lyme disease or other coinfections [11], we would not delay prophylaxis pending these results if the above criteria were met. (See 'Approach to prophylaxis' above.)

Testing of individual ticks for B. burgdorferi by polymerase chain reaction (PCR) is also available commercially; however, this type of testing is not recommended since the results do not affect clinical management [11]. As an example, if the tick has not been attached for at least 36 hours, it is unlikely to have transmitted disease and no prophylaxis should be offered, even if PCR is positive. In contrast, if the tick has been attached for ≥36 hours, then prophylaxis is recommended and a delay in initiation of prophylaxis while awaiting results of testing could be detrimental.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tick-borne infections (Lyme disease, ehrlichiosis, anaplasmosis, babesiosis, and Rocky Mountain spotted fever)".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Lyme disease (The Basics)")

●Beyond the Basics topics (see "Patient education: What to do after a tick bite to prevent Lyme disease (Beyond the Basics)" and "Patient education: Lyme disease symptoms and diagnosis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Tick vector – Most infections with Borrelia species, including Lyme disease, are transmitted to humans by a bite from an Ixodes tick in the nymphal stage (picture 1 and figure 2). The nymphal stage of the Ixodes tick is very small (about the size of a poppy seed) before feeding). (See 'Introduction' above and 'Tick size and appearance' above.)

●Transmission from tick to human – Borrelia burgdorferi is rarely transmitted within the first 48 to 72 hours of tick attachment. The likelihood of transmission is increased if the tick is engorged. (See 'Tick attachment' above.)

●Tick removal – In most cases, ticks are best removed with tweezers or protected fingers, pulling straight up with even pressure. (See 'Technique for tick removal' above.)

●Antibiotic prophylaxis following tick bite – We suggest antibiotic prophylaxis with a single dose of doxycycline be offered to nonpregnant adults (Grade 2B) and children (Grade 2C) who meet all of the following criteria after a tick bite to reduce the risk of developing subsequent Lyme disease (see 'Approach to prophylaxis' above):

•Attached tick identified as an adult or nymphal Ixodes scapularis tick (deer tick)

•Tick is estimated to have been attached for ≥36 hours (by degree of engorgement or time of exposure)

•Prophylaxis is begun within 72 hours of tick removal

•The bite occurs in a highly endemic area

•Doxycycline is not contraindicated

For patients who meet all of the above criteria, the recommended dose of doxycycline is 200 mg for adults and 4.4 mg/kg up to a maximum dose of 200 mg in children given as a single dose. Use of prophylaxis in children is based largely on the experience in adults. For those who cannot take doxycycline, we do not administer an alternate antibiotic.

●Prophylaxis during pregnancy – A single dose of doxycycline is very unlikely to cause harm to a fetus or mother, and there is no reason to believe the benefit of doxycycline prophylaxis would be any less during pregnancy. (See 'Approach to prophylaxis' above.)

●Patients who don’t receive prophylaxis – For patients who do not meet criteria for prophylaxis, we observe and treat only if signs or symptoms of Lyme disease (eg, erythema migrans) develop. We use this same approach for patients who cannot or do not want to take doxycycline prophylaxis.

●No role of serologic testing – There is no role for serologic testing at the time of the tick bite to detect a new Lyme infection. In addition, for asymptomatic patients, we typically do not perform routine follow-up testing four to six weeks after the bite since one would have to test many patients to find an asymptomatic seroconverter. and the benefit of antimicrobial therapy in asymptomatic patients is unclear. (See 'Serologic testing' above.)