Tick-borne diseases

Tick-borne diseases are caused by pathogens or toxins that are transmitted by ticks (and sometimes other vectors) and are typically associated with a specific geographical distribution. The clinically most significant tick-borne diseases in the US include Lyme disease, Rocky Mountain spotted fever, babesiosis, ehrlichiosis, anaplasmosis, tularemia, Colorado tick fever, tick-borne relapsing fever, southern tick‑associated rash illness, and tick paralysis. 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 respond well to treatment.

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

• Epidemiology: ∼ 5,500 cases were reported in 2018 ^[5]
• 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: Dermacentor species invade capillary endothelium → inflammation → small vessel vasculitis
• Clinical features ^[6]
  • 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)
• Diagnostics
  • CBC: typically normal WBC count, thrombocytopenia
  • Hyponatremia
  • Mildly ↑ hepatic transaminases
  • Confirmatory tests
    • PCR: detection of R. rickettsii DNA in a skin biopsy specimen or acute phase whole blood specimen
    • OR IFA test: four-fold increase in IgG-specific antibodies
    • OR immunohistochemical staining of R. rickettsii in a skin biopsy specimen
• Differential diagnosis
  • Meningococcemia
  • Lyme disease
  • Endocarditis
  • Hemorrhagic fever (e.g., Ebola fever, Hanta fever)
  • Vasculitis
• Treatment: doxycycline for all age groups ^[7]
  • Options during pregnancy:
    • Doxycycline ^[8]
    • Chloramphenicol during the 1^st and 2^nd trimester
• Prognosis: ^[9]
  • 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.

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

• 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. ^[10]
• Distribution: Midwestern (especially Minnesota and Wisconsin) and northeastern US
• Clinical features
  • Incubation period: 1–4 weeks ^[11]
  • 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. ^[12]
• 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 eaucleairensis
• 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 ^[13]
  • 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 ^[14]
    • Adults: ∼ 30% of cases
    • Children: ∼ 60% of cases
• Diagnostics
  • CBC: anemia, thrombocytopenia, leukopenia
  • Mild to moderate ↑ hepatic transaminases
  • Peripheral blood smear (with Wright stain or Giemsa stain): leukocytes with morulae (clustered inclusion bodies that resemble a mulberry) ^[13][15]
    • E. chaffeensis infection: morulae within monocytes
    • E. ewingii infection: morulae within granulocytes
  • Confirmatory test
    • Ehrlichia DNA detection by PCR of blood sample
    • OR IFA test shows a four-fold increase in IgG-specific antibodies between acute and convalescent serum samples
• Differential diagnosis: RMSF
• Treatment: doxycycline

• 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 ^[16]
  • Fever and other flu-like symptoms (headache, chills, muscle aches)
  • Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
  • Cough
  • Typically no rash
• Diagnostics
  • CBC: mild anemia, thrombocytopenia, leukopenia
  • Mild to moderate ↑ hepatic transaminases
  • Peripheral blood smear shows morulae within granulocytes.
  • Confirmatory test
    • Detection of Anaplasma DNA by PCR of blood sample
    • OR IFA test: four-fold increase in IgG-specific antibodies between acute and convalescent serum samples
• Treatment: doxycycline

• 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 ^[2]
  • Incubation period: typically 3–5 days (range 1–21 days) ^[17]
  • 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 ^[18]
  • Flu-like symptoms: often biphasic (fever remits after 2–4 days and returns 1–3 days later) ^[19]
  • 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 ^[19]
• 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 ^[20]
  • Recurring episodes of high fever for 3 days and an afebrile period of 7 days ^[4]
  • 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 ^[21]
  • Resembles early localized Lyme disease with erythema migrans-like lesion and possibly flu-like symptoms ^[21]
  • 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 (same as the treatment for Lyme disease) ^[22]

• 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).
• 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: ^[23]

1. Simon LV, West B, McKinney WP. Tick Paralysis. StatPearls. 2020 .
2. Rocky Mountain Spotted Fever (RMSF) - Epidemiology and Statistics. https://www.cdc.gov/rmsf/stats/index.html. Updated: April 7, 2020. Accessed: January 27, 2021.
3. Snowden J, Simonsen KA. Rickettsia Rickettsiae. StatPearls. 2020 .
4. Todd SR, Dahlgren FS, Traeger MS, et al. No Visible Dental Staining in Children Treated with Doxycycline for Suspected Rocky Mountain Spotted Fever. J Pediatr. 2015; 166 (5): p.1246-1251. doi: 10.1016/j.jpeds.2015.02.015 . | Open in Read by QxMD
5. Blanton LS. The Rickettsioses: A Practical Update.. Infect Dis Clin North Am. 2019; 33 (1): p.213-229. doi: 10.1016/j.idc.2018.10.010 . | Open in Read by QxMD
6. RMSF: deadly, but preventable. https://www.cdc.gov/ncezid/dvbd/media/rmsf.html. Updated: June 10, 2019. Accessed: January 27, 2021.
7. Belongia EA. Epidemiology and impact of coinfections acquired from Ixodes ticks.. Vector Borne Zoonotic Dis. 2002; 2 (4): p.265-73. doi: 10.1089/153036602321653851 . | Open in Read by QxMD
8. DPDx - Laboratory Identification of Parasites of Public Health Concern - Babesiosis. https://www.cdc.gov/dpdx/babesiosis/index.html. Updated: October 30, 2017. Accessed: January 28, 2021.
9. Vannier E, Gewurz BE, Krause PJ. Human babesiosis.. Infect Dis Clin North Am. 2008; 22 (3): p.469-88, viii-ix. doi: 10.1016/j.idc.2008.03.010 . | Open in Read by QxMD
10. CDC - Ehrlichiosis. https://www.cdc.gov/ticks/tickbornediseases/ehrlichiosis.html. Updated: October 1, 2020. Accessed: January 27, 2021.
11. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier Saunders ; 2015
12. Ismail N, Bloch KC, McBride JW. Human ehrlichiosis and anaplasmosis.. Clin Lab Med. 2010; 30 (1): p.261-92. doi: 10.1016/j.cll.2009.10.004 . | Open in Read by QxMD
13. Guzman N, Yarrarapu SNS, Beidas SO. Anaplasma Phagocytophilum (Anaplasmosis). StatPearls. 2020 .
14. Tularemia. https://www.cdc.gov/tularemia/index.html. Updated: September 27, 2016. Accessed: December 11, 2017.
15. WHO Guidelines on Tularaemia.
16. Colorado Tick Fever (CTF) - Symptoms & Treatment. https://www.cdc.gov/coloradotickfever/symptoms-treatment.html. Updated: December 3, 2018. Accessed: January 27, 2021.
17. Tickborne Diseases of the United States - Colorado Tick Fever. https://www.cdc.gov/ticks/tickbornediseases/ctf.html. Updated: January 10, 2019. Accessed: January 27, 2021.
18. Snowden J, Yarrarapu SNS, Oliver TI. Relapsing Fever. StatPearls. 2020 .
19. Tick-borne Relapsing Fever (TBRF). https://www.cdc.gov/relapsing-fever/clinicians/index.html. Updated: January 8, 2016. Accessed: December 11, 2017.
20. Southern Tick–Associated Rash Illness - STARI or Lyme?. https://www.cdc.gov/stari/disease/index.html. Updated: November 19, 2018. Accessed: January 27, 2021.
21. Southern Tick–Associated Rash Illness - Symptoms, Diagnosis and Treatment. https://www.cdc.gov/stari/symptoms/index.html. Updated: November 19, 2018. Accessed: January 27, 2021.
22. Tickborne Diseases of the United States: A Reference Manual for Health Care Providers.
23. Colorado Tick Fever. https://www.cdc.gov/coloradotickfever/healthcareproviders.html. Updated: January 13, 2015. Accessed: December 11, 2017.