Chapter 64: Tick-Borne Infections

• Children may be at higher risk for tick-borne infections than adults due to outdoor activities and potentially not noting attached ticks as readily as adults.

  • The most common tick-borne infection in the United States is Lyme disease, most common along the Atlantic seaboard and the upper Midwest.

  • The most common symptom of early localized Lyme disease is the erythema migrans (EM) (target) rash, which occurs within the first 2 weeks after the bite, at which time the antibody response is still negative (making localized Lyme a clinical diagnosis).

• Early disseminated Lyme disease occurs in approximately 15% of children several weeks after the tick bite. The most common symptom is multiple EM lesions; other manifestations can include facial nerve or other cranial nerve palsies and lymphocytic meningitis. Carditis is rare in children.

• Late Lyme disease can be seen as a complication of untreated early-stage Lyme. The most common symptom is relapsing large joint arthritis; neuropathy and meningoencephalitis are rare in children.

• The selection, route, and duration of antibiotic therapy depend upon the child's age, stage of Lyme disease, and site of infection. There is no convincing evidence for chronic Lyme disease, and courses of therapy longer than 4 weeks are not supported by the existing literature.

• Rocky Mountain spotted fever (RMSF) is a rickettsial disease most common in the southeastern and south central Midwest characterized by fever, headache, and rash. The rash begins as a maculopapular rash that then becomes petechial; it starts on the wrists/ankles and spreads centrally.

  • Multiorgan system failure and death can be seen with untreated RMSF, so for children suspected of having RMSF, treat empirically with doxycycline without waiting upon serologic confirmation.

• Ehrlichiosis is divided into two forms: human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HMA). The two entities cause very similar symptomatology, of fever, rash, myalgias, and headache, although HME can cause more severe symptoms than HMA. They both are treated with doxycycline.

  • Tularemia can be spread by contact with ticks or rabbits and other small mammals. A number of syndromes may be seen in patients, including ocular, lymphatic, and pharyngeal involvement. The treatment of choice is an aminoglycoside.

• Babesiosis causes a malaria-like illness in children; disease severity is highest in asplenic children. Diagnosis (peripheral smear) and treatment (clindamycin + quinine) are the same as for malaria.

Ticks can transmit a number of diseases to children; these include bacterial (Lyme, RMSF, ehrlichiosis, tularemia), protozoal (babesiosis), and viral (Colorado tick fever) pathogens. The index of suspicion for tick-borne pathogens should be high in children with unexplained fever or dermatologic findings: a child's play or other activities may put them at higher risk of contact with ticks than adults; the history of tick exposure infrequently is elicited; even if a child notes a tick, tick removal may not occur promptly or thoroughly; and children may become more ill with certain tick-borne diseases than adults.

Tick season will vary geographically (Table 64-1), but most tick-borne illnesses occur from April to October.¹ Tick-borne diseases may be seen throughout the year in warmer regions or after a mild winter as a hard freeze is needed to kill ticks. Ticks often need to be attached for up to 48 hours prior to transmission of disease. Thus, if a tick can be easily brushed off a child, it is unlikely to result in disease. Ticks tend to attach as in the larval or nymph forms, when they are very small, making detection challenging. Almost all disease-bearing ticks in the United States are hard ticks (rigid exoskeleton covering their dorsum). In male ticks, this covers the entire back, whereas it only covers the anterior aspect in females allowing the already larger-than-male tick to engorge more dramatically after feeding.¹ Knowledge of the appearance of different tick species (Fig. 64-1)² can help narrow the differential diagnosis.

Several strategies exist for tick prevention: environmental control such as spraying around the perimeter of yards; pet grooming and use of topical agents to rapidly remove adhered ticks; long pants tucked into socks and long-sleeved shirts; light-colored clothing to easily detect dark-bodied ticks. Chemical control includes spraying clothing with permethrin spray (which generally lasts 5–10 machine washings), and skin with DEET. Permethrin is more effective than DEET. Children should be checked for ticks after playing outside in endemic areas. Particular areas to check include the lower extremities and any site that is constricted by clothing (waist) or backpacks (axillae).

If ticks are encountered, viscous lidocaine may be applied to kill the tick and provide local anesthesia. Fine-tipped forceps are applied parallel to the skin as close to the skin as possible to grasp the head. The tick is pulled upward with even pressure. Twisting or jerking can result in mouthparts breaking off and remaining embedded in the skin. If mouthparts are retained, the area should be irrigated, but dissection to retrieve mouthparts is unnecessary.³ Parents should be encouraged to not apply heat or other irritants to ticks, as an irritated tick has a tendency to vomit and/or defecate, increasing the risk of disease transmission.

There are several common tick-borne diseases seen in the United States (see below) whereas others have very low prevalence such as Colorado tick fever and Q fever⁴ (included in Tables 64-2 and 64-3). (See Fig. 64-2 for algorithm for differentiating tick-borne illnesses.)

Lyme disease is caused by a spirochete, Borrelia burgdorferi and is transmitted by hard-bodied ticks of the Ixodes genus; these ticks can transmit babesiosis and anaplasmosis, occasionally resulting in a child having more than one tick-borne illness simultaneously. In one tick surveillance study in New England, over 50% of Ixodes ticks were infected with B. burgdorferi, 63% carried at least one pathogen, and 8% carried two pathogens.⁵ Ticks usually need to feed for 24 to 48 hours to transmit Lyme. Lyme disease is the most common tick-borne disease in the United States, with almost 250,000 cases reported from 1992 to 2006⁶; 30,000 cases were reported in 2010.⁴ Highest case rates are seen in New England (Table 64-1), where population expansion have put humans in more contact with deer, the primary reservoir of Lyme disease. Age distribution is bimodal with peaks from 5 to 9 and 55 to 59 years of age.⁶

The clinical stages and treatment of Lyme disease are described in Tables 64-2 and 64-4, respectively. The most common manifestation of early localized disease is EM which is blanchable, erythematous with central clearing (target rash), nontender, and minimally raised. EM usually begins within 7 to 10 days of tick infection.⁷ Constitutional symptoms including fever, headache, and myalgia, and negative serologies are common in early localized Lyme.

The second stage of Lyme infection, early disseminated disease, is characterized by multiorgan disease resulting from spirochete dissemination. This stage can include multiple EM lesions, episodes of arthralgias or myalgias, headaches, conjunctivitis, cranial nerve palsies (especially facial nerve palsy), and lymphocytic meningitis or meningoencephalitis.⁷ Carditis, presenting as atrioventricular block, can be seen but is rare in children. Diagnosis is serologic (Table 64-2). Treatment of early disseminated Lyme (Table 64-3) does not accelerate symptom resolution, but instead halts progression to late Lyme disease.

Late Lyme disease involves recurring large joint arthritis, neuroborreliosis (peripheral neuropathy, radiculopathy, paresthesias, or encephalopathy), and carditis (AV block, pericarditis, myocarditis, tachyarrhythmias, congestive heart failure, junctional rhythms, and prolonged QT intervals),⁸ in order of declining prevalence. The arthritis of Lyme disease most commonly affects large joints, especially the knee, although virtually any joint can be involved. Joint pain usually is out of proportion to the degree of swelling. The arthritis usually occurs months after the initial inoculation, lasts for 1 to 2 weeks and may recur.

The treatment of Lyme disease is contingent upon the child's age, stage of Lyme disease, and organ system involvement (Table 64-4).⁹ Children younger than 8 years of age typically receive amoxicillin in lieu of doxycycline. Treatment of early localized Lyme can result in blunting of the antibody response (false negatives). Central nervous system involvement aside from facial nerve palsies is usually treated with parenteral agents. Various symptoms have been attributed to “chronic Lyme disease” in the presence or even absence of serologic data. This has led to many patients being treated with prolonged courses of oral or parenteral therapy. There are no convincing data supporting the existence of chronic Lyme disease, nor are there data supporting courses of therapy longer than 4 weeks.¹⁰

The only postexposure prophylaxis after tick bites demonstrated to be efficacious has been after Ixodes tick bites in Lyme endemic regions.¹¹ Single-dose (200 mg) doxycycline has been recommended by some experts for children 8 years of age or older with an engorged deer tick suspected of feeding for 3 days or longer in an area of Lyme hyperendemicity and in which prophylaxis is started within 3 days of tick removal.⁹ The age, feeding duration, and timeliness of care, as well as the family's (or ED physician's) ability to accurately identify the tick species, provide barriers to the use of prophylaxis.

RMSF is caused by a rickettsial pathogen, Rickettsia rickettsii, and is transmitted by hard-bodied ticks of the Dermacentor genus; these ticks also can transmit ehrlichiosis, Q fever, and tularemia. Ticks usually need to feed 6 to 8 hours to transmit the pathogen. RMSF, belying its name, actually is more common in the southeastern and south/central Midwest (Table 64-1), with 60% of the almost 2000 cases reported in 2010 occurring in Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee.⁴ Children younger than 10 have the highest age-specific incidence of RMSF and account for up to 15% of deaths.¹² Rates of fatal RMSF are higher in children 5 to 9 years of age, the elderly, immunocompromised patients, and American Indians.¹³

Symptoms of RMSF usually appear approximately 7 days after tick exposure; a history of tick bite is elicited in approximately 50% of patients. The initial phase of RMSF infection is characterized by sudden onset of fever, malaise, and severe headache, with accompanying nonspecific influenza-like symptoms, thus, may be misdiagnosed as a viral syndrome during this phase. The classic triad of RMSF (fever, rash, and headache) is only seen in 3% of patients in the first 3 days, although it is usually seen in the majority of patients within the first 2 weeks.¹⁴ A rash usually appears between 2 and 5 days, although up to 10% of children may not develop a rash. The rash of RMSF usually begins as blanching, erythematous macules on the wrists and ankles, and spreads centripetally to the arms, legs, and trunks within hours. Palms and soles are also involved. By the end of the first week, the characteristic petechial rash will develop in 35% to 60% of patients. Some patients may develop neurologic symptoms such as meningismus, altered mental status, amnesia, coma, seizures, cranial nerve palsies, central deafness, and cortical blindness. Other manifestations are less commonly reported but include conjunctivitis, periorbital and peripheral edema, congestive heart failure, arrhythmias, myocarditis, shock, hepatomegaly, and jaundice.

Diagnosing RMSF can be difficult because the early signs and symptoms are often nonspecific; diagnosis is delayed in children without rash. No rapid tests exist, and antibody formation generally requires 7 to 10 days. Half of RMSF deaths occur during this time.¹² Ancillary laboratory support may include hyponatremia (as seen with most vasculitides) and thrombocytopenia. Due to the high mortality rate (20% if untreated, 5% if treated), empiric antibiotics should be started if RMSF is suspected. The treatment of choice is doxycycline, irrespective of a child's age (Table 64-3).¹⁵ In children with life-threatening illness, it may be reasonable to add an antibiotic against Neisseria meningitidis as this condition may be difficult to distinguish from RMSF.

There are two pathogens, HME caused by Ehrlichia chaffeensis or Ehrlichia ewingii, and HGA caused by Anaplasma phagocytophilum, collectively referred to as ehrlichiosis (termed “rashless RMSF”). They are caused by gram-negative cocci. Ehrlichiosis is transmitted by Ixodes ticks (HGA) or Dermacentor/Amblyomma ticks (HME) and thus occur in different locales (Table 64-1). There were 750 cases of HME and 1760 cases of HGA reported in 2010.⁴

The diseases are considered together given overlap in symptoms, diagnosis, and treatment.¹⁶ Both HGA and HME can cause fever, chills, and myalgias. Rash (ranging from maculopapular to petechial) and more severe disease (including pneumonitis, meningoencephalitis, or shock) are more common in HME. Although definitive diagnosis is contingent upon acute and convalescent serologies (Table 64-2), ancillary laboratory findings may include pancytopenia, elevated hepatic transaminases, and hyponatremia. Identification of morulae forms in peripheral blood smears is insensitive. The treatment of choice for both diseases is doxycycline, irrespective of patient age (Table 64-3).¹⁷ This would also treat RMSF, as HME and RMSF are found in the same geographic areas and carried by the same ticks. Children with HGA should be evaluated for Lyme disease or babesiosis if not all symptoms can be explained by HGA, as the Ixodes tick also transmits these pathogens.

Tularemia is caused by a gram-negative coccobacillus, Francisella tularensis and can be transmitted by dog or wood ticks (Dermacentor), the lone star tick (Amblyomma), or by lagomorphs (rabbits, hares) or other small mammals. Contact can include skinning animals, eating undercooked meat, or inadvertently running over carcasses with lawn equipment.^18,19 Vectors vary by season, with tick disease more common in the summer and rabbit-borne disease more common in the winter. Of note, the bacteria are quite hardy and can remain viable in frozen rabbit carcasses for several years. There were almost 1400 cases reported from 1990 to 2000 from 44 states; 4 states accounted for over one-half of all cases (Arkansas, Missouri, South Dakota, and Oklahoma). There is a bimodal age distribution, with peaks at 5 to 9 years of age and in the elderly.²⁰

Six categories of tularemia have been identified: ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal.²¹ The ulceroglandular form, the most common in children, is characterized by a slowly healing papular lesion at the tick bite, followed by painful inflammation to regional nodes; the latter may begin to spontaneously drain. The glandular form lacks the inoculation eschar. Oculoglandular disease involves severe conjunctivitis and preauricular lymphadenopathy; the differential for oculoglandular tularemia includes adenoviral infection and other causes of Parinaud's. Oropharyngeal tularemia may present as an exudative pharyngitis with painful cervical adenopathy. Typhoidal tularemia presents with abdominal pain and gastroenteritis symptoms, whereas pneumonic tularemia can present with fever, chest pain, and intrathoracic lymphadenopathy. Mortality rate for pneumonic tularemia can be as high as 60%.¹⁹

Laboratory findings of tularemia are nonspecific: leukocytosis, pyuria, and elevated hepatic transaminases may be observed. F. tularensis is difficult to isolate in blood or tissue cultures and can be hazardous to laboratory workers (who should be notified if tularemia is suspected). Consequently, tularemia is usually diagnosed by acute and convalescent serologic testing (Table 64-2). Aminoglycosides are currently first-line therapy for tularemia, with second-line therapy consisting of doxycycline, fluoroquinolones, or chloramphenicol (Table 64-3).²²

Babesiosis is caused by protozoa, Babesia microti, and is transmitted by the Ixodes tick. Of the 1100 cases reported in 2011, 97% occurred in seven states: Connecticut, Massachusetts, Minnesota, New Jersey, New York, Rhode Island, and Wisconsin.⁴ The primary reservoir species is the white-footed mouse. Unlike other tick-borne diseases, babesiosis is more common in adults, with less than 4% of reported cases occurring in children.²³ Transfusion-associated and transplacental transmission of babesiosis has been described. The symptoms, diagnosis, and treatment of babesiosis mirror those of malaria.

Babesiosis presents with an influenza-like illness: fever, chills, myalgia, headaches, and abdominal pain. Unlike influenza, symptoms may last weeks to months. Examination findings may include hepatosplenomegaly, whereas laboratory findings may reveal anemia and evidence of hemolysis, thrombocytopenia, elevated hepatic transaminases, and elevated blood urea nitrogen and creatinine. More severe disease is common in functionally or anatomically asplenic persons, who tend to have a high grade (>10%) of erythrocytes infected.²⁴

The definitive diagnosis (Table 64-2) is based upon the recognition of a Maltese cross appearance on peripheral smear.²⁵ Similar to malaria, thick and thin smears are sent. The former allow for estimation of the degree of parasitemia, whereas thin smears enable organism identification. Treatment (Table 64-3) is the same as for malaria, using clindamycin and quinine (or quinidine).²⁶ As quinine and quinidine can cause prolongation of the QT interval, baseline and serial electrocardiogram monitoring are reasonable. Exchange transfusion should be considered for asplenic patients, anyone with parasitemia over 10%, or patients with evidence of end-organ dysfunction.²⁴