Ticks, Including Tick Paralysis

Lyme Borreliosis

LB, or Lyme disease (see Chapter 241 ), is now the most common tick-borne infectious disease in the Northern Hemisphere and the most common arthropod-borne infectious disease in the United States. In the United States, LB is caused by Borrelia burgdorferi (sensu stricto), first identified as a novel bacterial spirochete in 1982, and transmitted to humans by Ixodes spp. hard ticks in US regional pockets, specifically the Northeast (I. scapularis), upper Midwest (I. scapularis), and Pacific Coast ( I. pacificus; see Figs. 296.2, 296.5, and 296.6 ). Although B. burgdorferi is the sole agent of LB in the United States, most cases of LB in Europe and northern Asia are caused by Borrelia afzelii and Borrelia garinii (see Table 296.1 ). Collectively, the three Borrelia species are often referred to as B. burgdorferi (sensu lato). Ticks usually acquire Borrelia infections as larvae or nymphs by blood-feeding on small reservoir hosts, most commonly birds and rodents, and may transmit LB to humans during blood-feeding, which may go unnoticed (see Fig. 296.2 ). Borrelia organisms are further maintained in nature as infected adult Ixodes ticks blood-feed on larger mammals, especially deer.

Unlike argasid or soft ticks, Ixodes ticks prefer temperate ecotonal zones of canopied forests abutting cleared scrub or grasslands and transmit B. burgdorferi to humans during outdoor exposures in such habitats. Because Borrelia spirochetes must migrate from the tick's midgut to the salivary gland during blood-feeding, tick attachments for less than 24 hours rarely result in LB in humans. After an incubation period of 1 to 2 weeks, the hallmark of spirochete transmission manifests as solitary erythema migrans, a maculopapular erythematous rash with a bull's-eye pattern, at the site of tick attachment ( Fig. 296.9 ). Erythema migrans in LB results from the subcutaneous centrifugal movement of the spirochetes from the bite sites to the central circulation and target organs (see Figs. 296.3 and 296.9 ). An erythema migrans -like rash also occurs in STARI at the site of A. americanum (Lone Star tick) attachment, but the underlying mechanisms responsible for the rash in STARI are unclear.

In a meta-analysis of 53 longitudinal studies of LB in the United States and Europe, Tibbles and Edlow reported that many patients did not recall a tick bite (74% in the United States, 36% in Europe), constitutional symptoms of low-grade fever (<39°C [102.2°F]) and headache were common but nausea and vomiting were rare, and a solitary erythema migrans lesion was the most common initial presentation of LB (81% in the United States, 88% in Europe). If LB is recognized and treated early in the erythema migrans stage, cure rates will exceed 90%, and outcomes will be excellent (see Table 296.2 ). Although deaths from LB are rare, 5% to 8% of patients may develop cardiac manifestations, and 15% to 20% of patients may develop neurologic manifestations.

In patients who previously had antibiotic-treated erythema migrans, reinfections with B. burgdorferi may occur in subsequent summers and will be again heralded by another erythema migrans lesion. Recent investigations by Nadelman and coworkers demonstrated that repeated episodes of pathognomonic erythema migrans in patients with previous appropriately treated early LB were due to reinfections and not to recurrences. However, persistent arthritis despite adequate antibiotic treatment of LB (now called post-infectious Lyme arthritis) may occur and was formerly referred to as chronic Lyme arthritis. Despite spirochetal elimination with antibiotic therapy, the proliferative synovitis of Lyme arthritis may extend for months to years and has been attributed to retained spirochetal fragments (such as B. burgdorferi peptoglycan) and/or autoimmune responses to these antigens and not to recurrent LB.

Unfortunately, some practitioners continue to diagnose patients who are suffering from a variety of generalized myofascial, arthritic, and neurologic pain conditions as having “chronic Lyme disease” and have prescribed long courses of oral and intravenous antibiotics despite evidence demonstrating that such therapies provide no improvement and can cause harm. In 2017, Marzec and coauthors reported a case series of five patients diagnosed with “chronic Lyme disease” who were then treated with protracted courses of antibiotics. The resulting complications from this unnecessary therapy included (1) septic shock from central venous catheter–associated bacteremia in two patients, with one fatality; (2) vertebral osteomyelitis in one patient; (3) intractable Clostridioides difficile (formerly Clostridium difficile ) colitis in one patient who later died from complications of amyotrophic lateral sclerosis (ALS); and (4) a paraspinal abscess that required surgical drainage in the last case.

Although the concept of chronic LB has been dispelled by carefully conducted clinical studies, lingering and unconfirmed associations continue to be made between LB cases and subsequent deaths due to four neurodegenerative disorders: ALS, Alzheimer disease (AD), multiple sclerosis (MS), and Parkinson disease (PD). If such associations truly existed, then the geographic distributions of LB cases and deaths from these four neurodegenerative disorders would be anticipated to significantly overlap. Forrester and coinvestigators compared LB incidence rates in each state from the National Notifiable Diseases Surveillance System during 2001–2010 with age-adjusted death rates for AD, ALS, MS, and PD obtained from the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database over the same reporting period. LB incidence per US state was not correlated with rates of death due to ALS, MS, or PD. However, an inverse correlation was detected between LB and AD. The authors concluded that their failure to accurately confirm any positive correlations between the geographic distribution of LB and the geographic distribution of deaths due to AD, ALS, MS, and PD provided further evidence that LB was not associated with the development of these common neurodegenerative conditions in an aging population.

The Jarisch-Herxheimer reaction (JHR), an inflammatory cytokine-mediated reaction to dying spirochetes with a worsening of presenting symptoms, vasodilation, and myocardial dysfunction, may occur during antibiotic treatment for LB but is more common after antibiotic therapy forTBRFs. There have been no reported deaths from JHR during antibiotic therapy for LB, and the very rare case fatalities from LB have been attributed to cardiac conduction abnormalities from myocarditis in untreated cases.

Southern Tick-Associated Rash Illness (STARI)

First recognized in 1998, STARI manifests initially as erythema migrans, as in LB, but occurs in regions in which B. burgdorferi is not endemic and follows the prolonged attachment of blood-feeding Lone Star ticks (A. americanum), more abundant in the southeastern and south central United States (see Fig. 296.3 ). Patients who are bitten by Lone Star ticks may develop LB-like erythema migrans rashes and occasionally develop milder constitutional symptoms than in LB, including fever, headache, fatigue, and generalized myalgias. However, unlike LB, STARI is not a reportable infectious disease and has no diagnostic serologic tests, such as enzyme-linked immunosorbent assays (ELISAs), immunofluorescence assays, and Western immunoblot assays. In addition, a microbiologic analysis of skin biopsy specimens obtained from the rashes of 30 patients in Missouri with clinical diagnoses of STARI failed to detect B. lonestari, suggesting that STARI could be caused by other pathogens. Because some patients have recovered from STARI without antibiotic treatment and there have been no long-term sequelae reported in STARI cases, some have questioned whether antibiotic therapy is indicated in STARI. Because distinguishing STARI from LB may be difficult, Wormser and coworkers have recommended that the differential diagnosis rely on a combination of regional exposures, clinical presentations, serologic results, and potential for long-term sequelae based on their comparison of LB cases from New York and STARI cases from Missouri. The investigators noted that the timing of rash onset was shorter (6 days) in STARI compared with LB (10 days) and that STARI patients were less likely to be symptomatic than LB patients. In addition, the STARI rash was more often circular with central clearing than the LB rash. Most authorities recommend antibiotic therapy for STARI with oral doxycycline or amoxicillin, following the same regimen as for LB to cover any missed diagnoses of LB with the potential for chronic arthritic and cardiac sequelae (see Table 296.2 ).

Tick-Borne Relapsing Fevers

The TBRFs (see Chapter 240 ) comprise a worldwide group of serious bacterial infections by Borrelia spirochetes after brief, painless, and usually unnoticed bites by Ornithodoros spp. argasid or soft ticks ( Fig. 296.10 ). Ornithodoros ticks prefer indoor living—in cabins, caves, and crevices—and quickly abandon warm-blooded rodent hosts for egg laying (see Table 296.1 ). Transovarian transmission of the TBRF spirochetes occurs commonly among all species and, unlike LB-causing Borrelia species, TBRF spirochetes are already present in the salivary glands at the onset of blood-feeding and do not need time to migrate from the gut to the mouthparts. The wild animal host reservoirs of TBRF are maintained in birds and several mammals, most commonly rodents. Adult ticks can live for as long as 15 to 20 years and survive without blood meals for several years.

The Ornithodoros species of soft ticks in the United States include Ornithodoros hermsii, Ornithodoros parkeri, and Ornithodoros turicatae (see Fig. 296.10 ). These soft ticks are widely distributed throughout the mountainous regions of the western half of the United States and southwestern Canada at elevations above 1500 m and transmit the spirochetes that cause TBRF ( Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae ). Humans typically come into contact with Ornithodoros soft ticks when they stay in frequently unoccupied and rodent-infested mountain cabins. The ticks emerge at night and feed briefly and unnoticed while the person is sleeping. Unlike the ixodid ticks, Ornithodoros ticks feed very rapidly, usually for less than 30 minutes, and always at night. The bites are painless as a result of local anesthetic-like chemicals in the tick saliva. The bite site is marked after a few days by a small red to violaceous papule with a central eschar. One spirochete is sufficient to initiate TBRF, and the infection rate after a single bite by an infected tick is more than 50%. The incubation period from tick bite to onset of the first febrile episode is 3 to 12 days. Since most people are unaware that they have been bitten, the history of potential regional exposures in high-altitude mountainous regions is essential to the correct diagnosis.

TBRF is defined clinically by the sudden onset of two or more episodes of high fever (>39°C [102.2°F]) spaced by afebrile periods of 4 to 14 days, with the first febrile episode lasting 3 to 6 days and the relapsing episodes lasting 1 to 3 days each. The first episode ends with a 15- to 30-minute “crisis” with tachycardia, hypertension, hyperpyrexia (as high as 43°C [109.4°F]), and rigors, followed by diaphoresis and defervescence. All febrile episodes are accompanied by nausea, headache, neck stiffness, myalgia, and arthralgia. The relapsing febrile episodes result from the growth of new spirochete populations in the blood to replace those killed by macrophages and cytokines. Most patients have splenomegaly, and 10% will have hepatomegaly. Direct neurologic involvement is more common than in LB and may include cranial nerve neuritis (especially cranial nerves VII and VIII), radiculopathy, and myelopathy. Myocarditis is also more common than in LB; may be complicated by adult respiratory distress syndrome, pulmonary edema, and cardiomegaly; and is often fatal.

Laboratory diagnostics include identifying the spirochetes microscopically on peripheral blood smears and detecting their nucleic acids using PCR assays. Thrombocytopenia (platelets <150 µL) is a common finding on the complete blood count. Most patients will have elevated aminotransferase levels, unconjugated bilirubin, and prolonged prothrombin and partial thromboplastin times.

Treatment strategies include tetracycline (500 mg or 12.5 mg/kg PO four times daily), or doxycycline (100 mg PO twice daily), or erythromycin (500 mg or 12.5 mg/kg PO four times daily for 10 days). Parenteral therapy with penicillin G or ceftriaxone is recommended for central nervous system (CNS) involvement.

The JHR is much more common, although rarely fatal, during treatment of TBRF than during treatment of LB and occurs in 30% to 40% of patients with TBRF. At present, no prophylactic strategies to reduce the severity of the JHR have proved beneficial or have been adequately tested in multiple clinical trials, including therapy with antipyretics, corticosteroids, or naloxone. Antispirochetal therapy for TBRF with penicillin instead of tetracycline has a slightly lower risk of associated JHR.