Tick-borne diseases

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Tick-borne diseases are predominantly caused by pathogens that are transmitted by ticks (and sometimes other vectors), except tick paralysis, which is caused by a neurotoxin produced by the tick itself. Tick-borne diseases are typically associated with specific geographical regions. The most clinically significant tick-borne diseases in the US include Lyme disease, Rocky Mountain spotted fever (RMSF), babesiosis, ehrlichiosis, anaplasmosis, tularemia, Colorado tick fever, tick-borne relapsing fever, southern tick‑associated rash illness,tick paralysis, and the more recently recognized alpha-gal syndrome. While manifestations of these conditions vary, common symptoms include fever, flu-like symptoms, and skin rashes. Most tick-borne diseases are treated with antibiotics and patients usually respond well to treatment.

Lyme disease is covered in more detail in its own article.

Background

• Epidemiology: ∼ 5500 cases were reported in 2018 ^[7]
• Pathogen: : Rickettsia rickettsii
• Vector
  • American dog tick (Dermacentor variabilis)
  • Rocky Mountain wood tick (Dermacentor andersoni)
  • Brown dog tick (Rhipicephalus sanguineus)
• Distribution
  • Cases reported across the contiguous US
  • Higher density especially in the midwestern, northeastern, and southern US
• Pathophysiology: Rickettsia species invade capillary endothelium → inflammation → small vessel vasculitis

Clinical features ^[8]

• Incubation period: 4–10 days
• Flu-like symptoms (e.g., fever, headache)
• Blanching maculopapular rash: begins on the wrists and ankles
  • Spreads to the trunk, palms, and soles
  • May become petechial and/or hemorrhagic
• Ankle and/or wrist swelling
• Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
• Meningitis, focal neurological deficits
• Rapid clinical deterioration with shock and multiorgan dysfunction (e.g., DIC)

The rash may be less obvious in dark-skinned individuals; therefore, close inspection and a high degree of clinical suspicion are required. ^[9]

Diagnostics ^[9][10][11]

RMSF is a clinical diagnosis.

• Laboratory studies ^[10]
  • CBC: typically normal WBC count, thrombocytopenia
  • BMP: ↓ Na, ↓ renal function in severe cases
  • Mildly ↑ AST and/or ALT
  • ↑ PT, ↑ INR, ↑ PTT
• Other supportive studies: ECG , CXR ^[9]
• Confirmatory studies: should be performed in all patients ^[11]
  • Indirect fluorescent antibody (IFA) test (gold standard): four-fold increase in IgG-specific antibodies
  • PCR: detection of R. rickettsii DNA in a skin biopsy specimen or acute phase whole blood specimen
  • Immunohistochemical staining of R. rickettsii in a skin biopsy specimen
• Lumbar puncture: to rule out meningitis in patients with neurological features ^[10]
  • Pleocytosis with lymphocytic or monocytic predominance
  • ↑ Protein
  • Normal glucose

Do not delay treatment while waiting for confirmatory studies and do not discontinue treatment based solely on the results. ^[11]

RMSF is a nationally notifiable disease in the United States. Contact the state or local health department if a potential case is suspected. ^[9]

Differential diagnosis ^[11]

• Meningococcemia
• Lyme disease
• Endocarditis
• Hemorrhagic fever (e.g., Ebola fever, Hanta fever)
• Vasculitis

Treatment

Initiate empiric antibiotic treatment immediately and consider consulting local infectious disease specialists. ^[11]

• Doxycycline ^[11][12]
• Supportive care in severe disease: e.g., broad-spectrum antibiotics for febrile patients in septic shock
• Options during pregnancy ^[11][13]
  • Doxycycline ^[13]
  • Chloramphenicol during the first and second trimester ^[11]

Treatment should be initiated as soon as RMSF is suspected, as it can be fatal if not treated early.

Disposition ^[11]

• Consider hospitalization for patients who:
  • Require supportive care
  • Have altered mental status
  • Are unable to adhere to follow-up
• Escalate to critical care unit based on clinical condition.
• In selected cases, consider discharge with oral antibiotics.

Prognosis ^[14]

• If treated within the first 5 days, patients typically fully recover without hospitalization.
• If treated after the first 5 days, symptoms are more severe and often require hospitalization. There is also a greater risk of long-term consequences of ischemia (e.g., amputations, paralysis, hearing loss, intellectual disability).
• If not treated early enough, the disease can be fatal.

• Pathogen: Babesia species (e.g., Babesia microti)
• Vector: deer tick (Ixodes scapularis)
  • Ixodes is also the vector for Borrelia burgdorferi and Anaplasma species.
  • Ticks are often coinfected; therefore, patients with babesiosis often also have Lyme disease. ^[15]
• Distribution: Midwestern (especially Minnesota and Wisconsin) and northeastern US
• Clinical features
  • Incubation period: 1–4 weeks ^[16]
  • Fever and other flu-like symptoms
  • Hemolytic anemia (e.g., dark urine, jaundice)
  • Mild splenomegaly and/or hepatomegaly
  • Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
  • Possibly petechiae, ecchymoses
  • Typically no rash
  • Asplenia increases the risk of severe disease. ^[17]
• Diagnostics
  • CBC: ↓ hematocrit, thrombocytopenia, ↑ reticulocyte count
  • Azotemia
  • Hemoglobinuria with/without hemosiderinuria
  • ↓ Serum haptoglobin
  • Mildly ↑ hepatic transaminases
  • Confirmatory tests
    • Peripheral blood smear showing Babesia as intraerythrocytic rings and/or Maltese cross
    • OR Babesia DNA detection by PCR of blood sample
    • OR Isolation of Babesia after animal inoculation
• Differential diagnosis
  • Malaria
  • Lyme disease
  • Ehrlichiosis
• Treatment
  • Mild disease: atovaquone PLUS azithromycin
  • Severe disease: quinine PLUS clindamycin

• Pathogens
  • Ehrlichia chaffeensis
  • Ehrlichia ewingii
  • Ehrlichia muris eauclairensis
• Vectors
  • Lone star tick (Amblyomma americanum): E. chaffeensis and E. ewingii
  • Deer tick (Ixodes scapularis): E. muris eauclairensis
• Distribution
  • Mainly east of the Rocky Mountains
  • Also some cases in the Southwest
• Clinical features
  • Incubation period: 1–2 weeks ^[18]
  • Flu-like symptoms (e.g., fever, myalgia)
  • Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
  • Hepatomegaly
  • Rarely, symptoms of meningitis and/or encephalitis (e.g., headache, altered mental status, stiff neck, neurological deficits)
  • Sometimes an erythematous maculopapular or petechial rash ^[19]
    • Adults: ∼ 30% of cases
    • Children: ∼ 60% of cases
• Diagnostics ^[11]
  • Ehrlichiosis is a clinical diagnosis.
  • Laboratory studies
    • CBC: anemia, thrombocytopenia, leukopenia
    • Mild to moderate ↑ AST and/or ALT
    • BMP: mild to moderate ↓ Na
  • Peripheral blood smear (with Wright stain or Giemsa stain): leukocytes with morulae (clustered inclusion bodies that resemble a mulberry) ; ^[11][20]
    • E. chaffeensis infection: morulae within monocytes
    • E. ewingii infection: morulae within granulocytes
  • Confirmatory tests: should be performed in all patients
    • IFA test (gold standard): four-fold increase in IgG-specific antibodies
    • PCR: detection of Ehrlichia DNA in a whole blood sample
• Differential diagnosis: RMSF
• Treatment: : doxycycline ^[11][12]
• Disposition: In selected cases, consider discharge with oral antibiotics. ^[11]

Ehrlichiosis is a nationally notifiable disease in the United States. Contact the state or local health department if a potential case is suspected. ^[9]

• Pathogen: Anaplasma phagocytophilum
• Vector
  • Deer tick (Ixodes scapularis)
  • Western black-legged tick (Ixodes pacificus)
  • Ixodes is also the vector for Borrelia burgdorferi and Babesia species, so coinfection is possible.
• Reservoir: deer and mice
• Distribution
  • Upper midwestern and northeastern US
  • Growing number of cases on the West Coast
• Clinical features
  • Incubation period: 1–2 weeks ^[21]
  • Fever and other flu-like symptoms (headache, chills, muscle aches)
  • Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
  • Cough
  • Typically no rash
• Diagnostics ^[11]
  • Anaplasmosis is a clinical diagnosis.
  • Laboratory studies
    • CBC: mild anemia, thrombocytopenia, leukopenia
    • Mild to moderate ↑ AST and/or ALT
  • Peripheral blood smear may show morulae within granulocytes.
  • Confirmatory tests: should be performed in all patients
    • IFA test (gold standard): four-fold increase in IgG-specific antibodies
    • PCR: detection of Anaplasma DNA in a whole blood sample
• Treatment: : doxycycline ^[11]
• Disposition: In selected cases, consider discharge with oral antibiotics. ^[11]

Anaplasmosis is a nationally notifiable disease in the United States. Contact the state or local health department if a potential case is suspected. ^[9]

• Pathogen: Francisella tularensis (facultative intracellular bacterium)
• Vector
  • Ticks (Amblyomma americanum, Dermacentor spp.)
  • Deer flies (Chrysops species)
  • Transmission without a vector is also possible via:
    • Inhalation of contaminated dust or aerosols (may result in pulmonary disease)
    • Ingestion of contaminated food or water
• Reservoir: rabbits, hares, and rodents (e.g., voles, muskrats)
• Distribution: all states except Hawaii
• Clinical features ^[3]
  • Incubation period: typically 3–5 days (range 1–21 days) ^[22]
  • Flu-like symptoms
  • High fever
  • Tender regional lymphadenopathy
  • Localized signs depending on manifestation:
    • Ulceroglandular tularemia (45–85%): skin ulcer at the entry site of F. tularensis
    • Glandular tularemia (10–25%): tender regional lymphadenopathy with no skin ulcer
    • Oculoglandular tularemia (<5%): unilateral conjunctival injection, pain, photophobia, tender preauricular and/or cervical lymphadenopathy
    • Oropharyngeal tularemia (<5%): sore throat, mouth ulcers, tonsillitis, tender cervical lymphadenopathy
    • Pneumonic tularemia (< 5%): nonproductive cough, pleuritic chest pain, dyspnea
    • Typhoidal tularemia (< 5%): hepatosplenomegaly
• Diagnostics
  • CBC: Normal or ↑ leukocyte count, thrombocytopenia
  • Hyponatremia
  • ↑ Serum transaminase levels and creatine phosphokinase
  • Myoglobinuria
  • Sterile pyuria
  • Confirmatory test
    • Positive culture (e.g., on charcoal yeast extract agar) from swabs/scrapings of skin lesions, pharyngeal swab, sputum specimen, gastric aspirate, and/or lymph node aspirate/biopsy
    • OR IFA test: four-fold increase in F. tularensis-specific antibody titers between acute and convalescent serum samples
  • Imaging (e.g., CXR, CT)
    • When pulmonary involvement is suspected
    • May show pulmonary infiltrates, hilar lymphadenopathy, and/or pleural effusion
• Differential diagnosis
  • Cat scratch disease
  • Brucellosis
• Treatment: streptomycin, gentamicin, doxycycline, OR ciprofloxacin
• Reporting: Tularemia is a notifiable condition.

• Pathogen: Colorado tick fever virus (CTFV), an RNA virus
• Vector: Rocky Mountain wood tick (Dermacentor andersoni)
• Distribution: western US
• Clinical features
  • Incubation period: 1–14 days ^[23]
  • Flu-like symptoms: often biphasic (fever remits after 2–4 days and returns 1–3 days later) ^[24]
  • Possibly conjunctival injection, pharyngeal erythema, and cervical lymphadenopathy
  • Petechial or maculopapular rash
• Diagnostics
  • CBC: leukopenia, thrombocytopenia
  • Peripheral blood smear may show atypical lymphocytes.
  • Confirmatory test
    • < 2 weeks after onset of symptoms onset: viral RNA detection by RT-PCR of blood sample
    • > 2 weeks after onset of symptoms: serum assay to detect CTFV-specific IgM antibodies ^[24]
• Treatment: only supportive management

• Pathogen: Borrelia hermsii
• Vector: Vector: Ornithodoros soft ticks (including O. hermsi, O. parkeri, O. turicata)
• Distribution: western US and Texas
• Clinical features
  • Incubation period: 4–18 days ^[25]
  • Recurring episodes of high fever for 3 days and an afebrile period of 7 days ^[5]
  • Arthralgia (∼ 70%)
  • Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain, diarrhea)
  • Less commonly
    • Hepatic manifestations (e.g., jaundice, hepatosplenomegaly)
    • Symptoms of meningitis (e.g., confusion, photophobia, neck pain, nuchal rigidity)
  • Macular rash or scattered petechiae may occur.
• Diagnostics
  • CBC: normal or ↑ leukocyte count, thrombocytopenia
  • Mild ↑ in serum bilirubin level
  • Slightly prolonged PT and aPTT
  • ↑ ESR
  • Confirmatory test
    • Direct observation of spirochetes in peripheral blood smears, bone marrow, or CSF with Giemsa-Wright stain, acridine orange stain, or dark-field microscopy
    • OR IFA test: four-fold increase in Borrelia-specific antibody titers between acute and convalescent serum samples
• Treatment
  • No CNS involvement:
    • First line: tetracycline
    • Second line: erythromycin
  • CNS involvement: ceftriaxone

• Pathogen: unknown
• Vector: Lone star tick (Amblyomma americanum)
• Distribution: southeastern and eastern US
• Clinical features
  • Incubation period: ∼ 7 days ^[26]
  • Resembles early localized Lyme disease with erythema migrans-like lesion and possibly flu-like symptoms ^[26]
  • Not associated with clinical features of early disseminated (e.g., arthralgia, facial nerve palsy, cardiac complications) or late Lyme disease (e.g., progressive encephalomyelitis).
• Diagnostics: Clinically determined by ruling out Lyme disease.
• Treatment: doxycycline, amoxicillin, OR cefuroxime axetil (See “Treatment of Lyme disease” for details.) ^[27]

• Definition: a rare syndrome caused by the salivary neurotoxin of certain ticks, characterized by acute ataxia, that progresses to ascending paralysis
• Epidemiology: most commonly occurs in children and women
• Etiology: > 40 tick species are associated with tick paralysis
  • Most common in the US: Dermacentor species (e.g., Rocky Mountain wood tick)
  • Others: Lone star tick (Amblyomma americanum), deer tick (Ixodes scapularis)
• Distribution: most commonly in the Rocky Mountains and northwestern US
• Pathophysiology
  • Paralysis is caused by tick neurotoxin, which is produced in the tick's salivary gland and introduced into the person's blood.
  • Possible mechanisms:
    • Dermacentor species: inhibition of sodium flux across axonal membranes
    • Ixodes species: inhibition of acetylcholine release at the neuromuscular junction
  • Tick neurotoxin → impairment of motor nerve transmission → muscle weakness → paralysis
• Clinical features
  • Symptoms begin within 2–7 days of the initial tick bite.
  • Typically starts with weakness in the lower extremities
  • Escalates to ascending flaccid paralysis that progresses rapidly and can lead to respiratory failure due to respiratory muscle weakness
  • Sensory deficits are usually absent.
  • Cranial nerve palsies may occur (e.g., CN III palsy).
  • No fever or rash
• Diagnostics
  • Clinically determined by finding a tick attached to the body and/or ruling out other tick-borne diseases associated with neurological deficits (e.g., Lyme disease, Q fever).
  • CSF examination is usually normal in tick-borne paralysis.
• Differential diagnosis
  • Guillain-Barré syndrome
  • Botulism
  • Poliomyelitis
  • Myasthenia gravis
  • Spinal cord lesion
• Treatment
  • Locate and remove the tick.
  • Supportive therapy (e.g., ventilatory support for patients with respiratory failure)

References: ^[28]

• Definition: an allergic reaction to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) found on the cells of nonprimate mammals (e.g., cows, pigs, lambs) that is thought to occur after a parasitic infection or the bite of a tick ^[6]
• Etiology ^[6]
  • Lone star tick (Amblyomma americanum)
  • Parasitic infections (e.g., ascariasis) have also been implicated.
• Reservoir: deer (principal host)
• Distribution ^[6]
  • US: Midwest, southeastern and eastern US
  • Worldwide: Western Europe, South Africa, Japan, Australia
• Pathophysiology
  • Sensitization: Lone star tick bite or parasitic infection → production of IgE antibodies against alpha-gal
  • Type I hypersensitivity: consumption of mammalian-derived products in a sensitized individual → alpha-gal absorbed in GI tract enters the circulation → IgE against alpha-gal → mast-cell degranulation
• Clinical features ^[6]
  • Typically present 2–6 hours after ingestion
  • May be asymptomatic ^[6]
  • GI features
    • Abdominal pain (most common)
    • Vomiting
    • Diarrhea
  • Mucocutaneous features: urticaria, angioedema
  • Anaphylaxis (most severe presentation)
• Diagnosis: primarily a clinical diagnosis, but may be supported by the following ^[6]
  • Positive clinical response after ≥ 1 month of alpha-gal avoidance
  • Serum: ↑ IgE against alpha-gal titers
• Management: should be specialist-guided (e.g., gastroenterology, immunology) ^[6]
  • Alpha-gal avoidance
    • Diet: Avoid mammalian-derived meats and products.
    • Medical products: e.g., cetuximab, pancreatic enzymes ^[6]
  • Pharmacotherapy: Consider immediately after exposure.
    • Oral antihistamines (e.g., diphenhydramine ) ^[6]
    • AND/OR epinephrine autoinjector
  • Referral: Consider consulting immunology and/or allergy specialists for patients with cutaneous or systemic symptoms (e.g., hypotension, urticaria).
• Prognosis: Sensitization to alpha-gal may fade or resolve over time. ^[6]
• Prevention: tick bite prevention (further tick bites may worsen the allergy)

Alpha-gal does not cause anemia, GI bleeding, or weight loss. If these features are present consider alternative diagnoses. ^[6]