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Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States

Published:October 09, 2021DOI:https://doi.org/10.1016/j.wem.2021.09.001
      The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the prevention and management of tick-borne illness (TBI). Recommendations are graded based on quality of supporting evidence according to criteria put forth by the American College of Chest Physicians. The guidelines include a brief review of the clinical presentation, epidemiology, prevention, and management of TBI in the United States, with a primary focus on interventions that are appropriate for resource-limited settings. Strong recommendations are provided for the use of DEET, picaridin, and permethrin; tick checks; washing and drying clothing at high temperatures; mechanical tick removal within 36 h of attachment; single-dose doxycycline for high-risk Lyme disease exposures versus “watchful waiting;” evacuation from backcountry settings for symptomatic tick exposures; and TBI education programs. Weak recommendations are provided for the use of light-colored clothing; insect repellents other than DEET, picaridin, and permethrin; and showering after exposure to tick habitat. Weak recommendations are also provided against passive methods of tick removal, including the use of systemic and local treatments. There was insufficient evidence to support the use of long-sleeved clothing and the avoidance of tick habitat such as long grasses and leaf litter. Although there was sound evidence supporting Lyme disease vaccination, a grade was not offered as the vaccine is not currently available for use in the United States.

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      References

        • Eisen R.J.
        • Kugeler K.J.
        • Eisen L.
        • Beard C.B.
        • Paddock C.D.
        Tick-borne zoonoses in the United States: persistent and emerging threats to human health.
        ILAR J. 2017; 58: 319-335
      1. Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System, 2019 Annual Tables of Infectious Disease Data, Atlanta, GA2021
        • Kugeler K.J.
        • Schwartz A.M.
        • Delorey M.J.
        • Mead P.S.
        • Hinckley A.F.
        Estimating the frequency of Lyme disease diagnoses, United States, 2010–2018.
        Emerg Infect Dis. 2021; 27: 616-619
        • Rosenberg R.
        • Lindsey N.P.
        • Fischer M.
        • Gregory C.J.
        • Hinckley A.F.
        • Mead P.S.
        • et al.
        Vital signs: trends in reported vectorborne disease cases—United States and Territories, 2004–2016.
        MMWR Morb Mortal Wkly Rep. 2018; 67: 496-501
        • Diaz J.H.
        Emerging tickborne viral infections: what wilderness medicine providers need to know.
        Wilderness Environ Med. 2020; 31: 489-497
        • Pujalte G.G.A.
        • Marberry S.T.
        • Libertin C.R.
        Tick-borne illnesses in the United States.
        Prim Care. 2018; 45: 379-391
        • Guyatt G.
        • Gutterman D.
        • Baumann M.H.
        • Addrizzo-Harris D.
        • Hylek E.M.
        • Phillips B.
        • et al.
        Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force.
        Chest. 2006; 129: 174-181
        • Centers for Disease Control and Prevention
        Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers.
        5th ed. Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA2018
        • Richter D.
        • Matuschka F.R.
        • Spielman A.
        • Mahadevan L.
        How ticks get under your skin: insertion mechanics of the feeding apparatus of Ixodes ricinus ticks.
        Proc Biol Sci. 2013; 280: 20131758
        • Gayle A.
        • Ringdahl E.
        Tick-borne diseases.
        Am Fam Physician. 2001; 64: 461-466
        • Falco R.C.
        • Fish D.
        • Piesman J.
        Duration of tick bites in a Lyme disease-endemic area.
        Am J Epidemiol. 1996; 143: 187-192
        • Levin M.L.
        • Ford S.L.
        • Hartzer K.
        • Krapiunaya L.
        • Stanley H.
        • Snellgrove A.N.
        Minimal duration of tick attachment sufficient for transmission of infectious Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) by its primary vector Dermacentor variabilis (Acari: Ixodidae): duration of rickettsial reactivation in the vector revisited.
        J Med Entomol. 2020; 57: 585-594
        • Roome A.
        • Spathis R.
        • Hill L.
        • Darcy J.M.
        • Garruto R.M.
        Lyme disease transmission risk: seasonal variation in the built environment.
        Healthcare (Basel). 2018; 6: 84
        • Ostfeld R.S.
        • Brunner J.L.
        Climate change and Ixodes tick-borne diseases of humans.
        Philos Trans R Soc Lond B Biol Sci. 2015; 370: 20140051
        • Wallace D.
        • Ratti V.
        • Kodali A.
        • Winter J.M.
        • Ayres M.P.
        • Chipman J.W.
        • et al.
        Effect of rising temperature on Lyme disease: Ixodes scapularis population dynamics and Borrelia burgdorferi transmission and prevalence.
        Can J Infect Dis Med Microbiol. 2019; : 9817930
        • Pfäffle M.
        • Littwin N.
        • Muders S.V.
        • Petney T.N.
        The ecology of tick-borne diseases.
        Int J Parasitol. 2013; 43: 1059-1077
        • Sonenshine D.E.
        Range expansion of tick disease vectors in North America: implications for spread of tick-borne disease.
        Int J Environ Res Public Health. 2018; 15: 478
        • Hofhuis A.
        • Herremans T.
        • Notermans D.W.
        • Sprong H.
        • Fonville M.
        • van der Giessen J.W.
        • et al.
        A prospective study among patients presenting at the general practitioner with a tick bite or erythema migrans in the Netherlands.
        PLoS One. 2013; 8e64361
        • Swanson S.J.
        • Neitzel D.
        • Reed K.D.
        • Belongia E.A.
        Coinfections acquired from Ixodes ticks.
        Clin Microbiol Rev. 2006; 19: 708-727
        • Moutailler S.
        • Valiente Moro C.
        • Vaumourin E.
        • Michelet L.
        • Tran F.H.
        • Devillers E.
        • et al.
        Co-infection of ticks: the rule rather than the exception.
        PLoS Negl Trop Dis. 2016; 10e0004539
        • Diuk-Wasser M.A.
        • Vannier E.
        • Krause P.J.
        Coinfection by Ixodes tick-borne pathogens: ecological, epidemiological, and clinical consequences.
        Trends Parasitol. 2016; 32: 30-42
        • Nadelman R.B.
        • Wormser G.P.
        Lyme borreliosis.
        Lancet. 1998; 352: 557-565
        • Feder H.M.
        • Whitaker D.L.
        Misdiagnosis of erythema migrans.
        Am J Med. 1995; 99: 412-419
        • Scheffold N.
        • Herkommer B.
        • Kandolf R.
        • May A.E.
        Lyme carditis: diagnosis, treatment and prognosis.
        Dtsch Arztebl Int. 2015; 112: 202-208
        • Fish A.E.
        • Pride Y.B.
        • Pinto D.S.
        Lyme carditis.
        Infect Dis Clin North Am. 2008; 22: 275-288
        • Molloy P.J.
        • Telford S.R.
        • Chowdri H.R.
        • Lepore T.J.
        • Gugliotta J.L.
        • Weeks K.E.
        • et al.
        Borrelia miyamotoi disease in the northeastern United States: a case series.
        Ann Intern Med. 2015; 163: 91-98
        • Pritt B.S.
        • Respicio-Kingry L.B.
        • Sloan L.M.
        • Schriefer M.E.
        • Replogle A.J.
        • Bjork J.
        • et al.
        Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States.
        Int J Syst Evol Microbiol. 2016; 66: 4878-4880
        • Regan J.J.
        • Traeger M.S.
        • Humpherys D.
        • Mahoney D.L.
        • Martinez M.
        • Emerson G.L.
        • et al.
        Risk factors for fatal outcome from Rocky Mountain spotted fever in a highly endemic area—Arizona, 2002–2011.
        Clin Infect Dis. 2015; 60: 1659-1666
        • Platts-Mills T.A.E.
        • Li R.C.
        • Keshavarz B.
        • Smith A.R.
        • Wilson J.M.
        Diagnosis and management of patients with the α-gal syndrome.
        J Allergy Clin Immunol Pract. 2020; 8: 15-23.e1
        • Richardson M.
        • Khouja C.
        • Sutcliffe K.
        Interventions to prevent Lyme disease in humans: a systematic review.
        Prev Med Rep. 2019; 13: 16-22
        • Centers for Disease Control and Prevention
        Protecting yourself from ticks and mosquitoes.
        National Institute for Occupational Health and Safety, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA2010: 2010-2119
        • Stjernberg L.
        • Berglund J.
        Detecting ticks on light versus dark clothing.
        Scand J Infect Dis. 2005; 37: 361-364
        • Ley C.
        • Olshen E.M.
        • Reingold A.L.
        Case-control study of risk factors for incident Lyme disease in California.
        Am J Epidemiol. 1995; 142: S39-S47
        • Fradin M.S.
        • Day J.F.
        Comparative efficacy of insect repellents against mosquito bites.
        N Engl J Med. 2002; 347: 13-18
        • Ogawa K.
        • Komagata O.
        • Hayashi T.
        • Itokawa K.
        • Morikawa S.
        • Sawabe K.
        • et al.
        Field and laboratory evaluations of the efficacy of DEET repellent against Ixodes ticks.
        Jpn J Infect Dis. 2016; 69: 131-134
        • Jensenius M.
        • Pretorius A.M.
        • Clarke F.
        • Myrvang B.
        Repellent efficacy of four commercial DEET lotions against Amblyomma hebraeum (Acari: Ixodidae), the principal vector of Rickettsia africae in southern Africa.
        Trans R Soc Trop Med Hyg. 2005; 99: 708-711
        • Meng H.
        • Li A.Y.
        • Costa Junior L.M.
        • Castro-Arellano I.
        • Liu J.
        Evaluation of DEET and eight essential oils for repellency against nymphs of the lone star tick, Amblyomma americanum (Acari: Ixodidae).
        Exp Appl Acarol. 2016; 68: 241-249
        • Swale D.R.
        • Bloomquist J.R.
        Is DEET a dangerous neurotoxicant?.
        Pest Manag Sci. 2019; 75: 2068-2070
        • McGready R.
        • Hamilton K.A.
        • Simpson J.A.
        • Cho T.
        • Luxemburger C.
        • Edwards R.
        • et al.
        Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy.
        Am J Trop Med Hyg. 2001; 65: 285-289
        • Koren G.
        • Matsui D.
        • Bailey B.
        DEET-based insect repellents: safety implications for children and pregnant and lactating women.
        CMAJ. 2003; 169: 209-212
        • Abdel-Ghaffar F.
        • Al-Quraishy S.
        • Mehlhorn H.
        Length of tick repellency depends on formulation of the repellent compound (icaridin=Saltidin): tests on Ixodes persulcatus and Ixodes ricinus placed on hands and clothes.
        Parasitol Res. 2015; 114: 3041-3045
        • Heng S.
        • Sluydts V.
        • Durnez L.
        • Mean V.
        • Polo K.
        • Tho S.
        • et al.
        Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia.
        PLoS One. 2017; 12e0172566
        • Miller N.J.
        • Rainone E.E.
        • Dyer M.C.
        • González M.L.
        • Mather T.N.
        Tick bite protection with permethrin-treated summer-weight clothing.
        J Med Entomol. 2011; 48: 327-333
        • Faulde M.K.
        • Rutenfranz M.
        • Keth A.
        • Hepke J.
        • Rogge M.
        • Görner A.
        Pilot study assessing the effectiveness of factory-treated, long-lasting permethrin-impregnated clothing for the prevention of tick bites during occupational tick exposure in highly infested military training areas, Germany.
        Parasitol Res. 2015; 114: 671-678
        • Roßbach B.
        • Kegel P.
        • Zier U.
        • Niemietz A.
        • Letzel S.
        Protective efficacy of permethrin-treated trousers against tick infestation in forestry workers.
        Ann Agric Environ Med. 2014; 21: 712-717
        • Vaughn M.F.
        • Funkhouser S.W.
        • Lin F.C.
        • Fine J.
        • Juliano J.J.
        • Apperson C.S.
        • et al.
        Long-lasting permethrin impregnated uniforms: A randomized-controlled trial for tick bite prevention.
        Am J Prev Med. 2014; 46: 473-480
        • Evans S.R.
        • Korch G.W.
        • Lawson M.A.
        Comparative field evaluation of permethrin and DEET-treated military uniforms for personal protection against ticks (Acari).
        J Med Entomol. 1990; 27: 829-834
        • Bissinger B.W.
        • Apperson C.S.
        • Watson D.W.
        • Arellano C.
        • Sonenshine D.E.
        • Roe R.M.
        Novel field assays and the comparative repellency of BioUD, DEET and permethrin against Amblyomma americanum.
        Med Vet Entomol. 2011; 25: 217-226
        • Schreck C.E.
        • Haile D.G.
        • Kline D.L.
        The effectiveness of permethrin and DEET, alone or in combination, for protection against Aedes taeniorhynchus.
        Am J Trop Med Hyg. 1984; 33: 725-730
        • Flor-Weiler L.B.
        • Behle R.W.
        • Stafford K.C.
        Susceptibility of four tick species, Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus (Acari: Ixodidae), to nootkatone from essential oil of grapefruit.
        J Med Entomol. 2011; 48: 322-326
        • Semmler M.
        • Abdel-Ghaffar F.
        • Al-Rasheid K.A.
        • Mehlhorn H.
        Comparison of the tick repellent efficacy of chemical and biological products originating from Europe and the USA.
        Parasitol Res. 2011; 108: 899-904
        • van der Heijden A.
        • Mulder B.C.
        • Poortvliet P.M.
        • van Vliet A.J.H.
        Social-cognitive determinants of the tick check: a cross-sectional study on self-protective behavior in combatting Lyme disease.
        BMC Public Health. 2017; 17: 900
        • Vázquez M.
        • Muehlenbein C.
        • Cartter M.
        • Hayes E.B.
        • Ertel S.
        • Shapiro E.D.
        Effectiveness of personal protective measures to prevent Lyme disease.
        Emerg Infect Dis. 2008; 14: 210-216
        • Connally N.P.
        • Durante A.J.
        • Yousey-Hindes K.M.
        • Meek J.I.
        • Nelson R.S.
        • Heimer R.
        Peridomestic Lyme disease prevention: results of a population-based case-control study.
        Am J Prev Med. 2009; 37: 201-206
        • Carroll J.F.
        A cautionary note: survival of nymphs of two species of ticks (Acari: Ixodidae) among clothes laundered in an automatic washer.
        J Med Entomol. 2003; 40: 732-736
        • Nelson C.A.
        • Hayes C.M.
        • Markowitz M.A.
        • Flynn J.J.
        • Graham A.C.
        • Delorey M.J.
        • et al.
        The heat is on: killing blacklegged ticks in residential washers and dryers to prevent tickborne diseases.
        Ticks Tick Borne Dis. 2016; 7: 958-963
        • Shakman R.A.
        Tick removal.
        West J Med. 1984; 140: 99
        • Pavlovic M.
        • Alakeel A.
        • Frances C.
        Tick removal with liquid nitrogen.
        JAMA Dermatol. 2013; 149: 633
        • Karras D.J.
        Tick removal.
        Ann Emerg Med. 1998; 32: 519
        • Jang Y.H.
        • Moon S.Y.
        • Lee W.J.
        • Lee S.J.
        • Kim D.W.
        Mildly heated forceps: a useful instrument for easy and complete removal of ticks on the skin.
        J Am Acad Dermatol. 2014; 71: e199-e200
        • Benforado J.M.
        Removal of ticks.
        JAMA. 1984; 252: 3368
        • Celenza A.
        • Rogers I.R.
        The “knot method” of tick removal.
        Wilderness Environ Med. 2002; 13: 179-180
        • Roupakias S.
        • Mitsakou P.
        • Al Nimer A.
        Surgical tick removal.
        Wilderness Environ Med. 2012; 23: 97-99
        • Schneider L.A.
        • Dissemond J.
        When professional forceps are not available: efficient tick removal using a no. 15 scalpel as a spade.
        Eur J Dermatol. 2015; 25: 193-194
        • Stewart R.L.
        • Burgdorfer W.
        • Needham G.R.
        Evaluation of three commercial tick removal tools.
        Wilderness Environ Med. 1998; 9: 137-142
        • Duscher G.G.
        • Peschke R.
        • Tichy A.
        Mechanical tools for the removal of Ixodes ricinus female ticks: differences of instruments and pulling or twisting?.
        Parasitol Res. 2012; 111: 1505-1511
        • Needham G.R.
        Evaluation of five popular methods for tick removal.
        Pediatrics. 1985; 75: 997-1002
        • Akin Belli A.
        • Dervis E.
        • Kar S.
        • Ergonul O.
        • Gargili A.
        Revisiting detachment techniques in human-biting ticks.
        J Am Acad Dermatol. 2016; 75: 393-397
        • Ghirga G.
        • Ghirga P.
        Effective tick removal with a fishing line knot.
        Wilderness Environ Med. 2010; 21: 270-271
        • Kahl O.
        • Janetzki-Mittmann C.
        • Gray J.S.
        • Jonas R.
        • Stein J.
        • de Boer R.
        Risk of infection with Borrelia burgdorferi sensu lato for a host in relation to the duration of nymphal Ixodes ricinus feeding and the method of tick removal.
        Zentralbl Bakteriol. 1998; 287: 41-52
        • Oteo J.A.
        • Martinez de Artola V.
        • Gomez-Cadinanos R.
        • Casas J.M.
        • Blanco J.R.
        • Rosel L.
        [Evaluation of methods of tick removal in human ixodidiasis].
        Rev Clin Esp. 1996; 196: 584-587
        • De Boer R.
        • van den Bogaard A.E.
        Removal of attached nymphs and adults of Ixodes ricinus (Acari: Ixodidae).
        J Med Entomol. 1993; 30: 748-752
        • Lee M.D.
        • Sonenshine D.E.
        • Counselman F.L.
        Evaluation of subcutaneous injection of local anesthetic agents as a method of tick removal.
        Am J Emerg Med. 1995; 13: 14-16
        • Sheele J.M.
        • Ford L.R.
        • Tse A.
        • Chidester B.
        • Byers P.A.
        • Sonenshine D.E.
        The use of ivermectin to kill Ixodes scapularis ticks feeding on humans.
        Wilderness Environ Med. 2014; 25: 29-34
        • Coleman N.
        • Coleman S.
        Methods of tick removal: a systemic review of the literature.
        AMJ. 2017; 10: 53-62
        • Wormser G.P.
        • Dattwyler R.J.
        • Shapiro E.D.
        • Halperin J.J.
        • Steere A.C.
        • Klempner M.S.
        • et al.
        The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.
        Clin Infect Dis. 2006; 43: 1089-1134
        • Shapiro E.D.
        Clinical practice. Lyme disease.
        N Engl J Med. 2014; 370: 1724-1731
        • Sood S.K.
        • Salzman M.B.
        • Johnson B.J.
        • Happ C.M.
        • Feig K.
        • Carmody L.
        • et al.
        Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.
        J Infect Dis. 1997; 175: 996-999
        • Piesman J.
        • Mather T.N.
        • Sinsky R.J.
        • Spielman A.
        Duration of tick attachment and Borrelia burgdorferi transmission.
        J Clin Microbiol. 1987; 25: 557-558
        • Piesman J.
        • Maupin G.O.
        • Campos E.G.
        • Happ C.M.
        Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method.
        J Infect Dis. 1991; 163: 895-897
        • Piesman J.
        Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks.
        J Infect Dis. 1993; 167: 1082-1085
        • Cook M.J.
        Lyme borreliosis: a review of data on transmission time after tick attachment.
        Int J Gen Med. 2014; 8: 1-8
        • Nadelman R.B.
        • Nowakowski J.
        • Fish D.
        • Falco R.C.
        • Freeman K.
        • McKenna D.
        • et al.
        Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite.
        N Engl J Med. 2001; 345: 79-84
        • Warshafsky S.
        • Lee D.H.
        • Francois L.K.
        • Nowakowski J.
        • Nadelman R.B.
        • Wormser G.P.
        Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis.
        J Antimicrob Chemother. 2010; 65: 1137-1144
        • Harms M.G.
        • Hofhuis A.
        • Sprong H.
        • Bennema S.C.
        • Ferreira J.A.
        • Fonville M.
        • et al.
        A single dose of doxycycline after an Ixodes ricinus tick bite to prevent Lyme borreliosis: an open-label randomized controlled trial.
        J Infect. 2021; 82: 98-104
        • Lantos P.M.
        • Rumbaugh J.
        • Bockenstedt L.K.
        • Falck-Ytter Y.T.
        • Aguero-Rosenfeld M.E.
        • Auwaerter P.G.
        • et al.
        Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease.
        Clin Infect Dis. 2021; 72: 1-8
        • Gentile D.A.
        • Morris J.A.
        • Schimelpfenig T.
        • Bass S.M.
        • Auerbach P.S.
        Wilderness injuries and illnesses.
        Ann Emerg Med. 1992; 21: 853-861
        • Leemon D.
        • Schimelpfenig T.
        Wilderness injury, illness, and evacuation: National Outdoor Leadership School’s incident profiles, 1999–2002.
        Wilderness Environ Med. 2003; 14: 174-182
        • McIntosh S.E.
        • Leemon D.
        • Visitacion J.
        • Schimelpfenig T.
        • Fosnocht D.
        Medical incidents and evacuations on wilderness expeditions.
        Wilderness Environ Med. 2007; 18: 298-304
        • Sigal L.H.
        • Zahradnik J.M.
        • Lavin P.
        • Patella S.J.
        • Bryant G.
        • Haselby R.
        • et al.
        A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.
        N Engl J Med. 1998; 339: 216-222
        • Piesman J.
        • Eisen L.
        Prevention of tick-borne diseases.
        Annu Rev Entomol. 2008; 53: 323-343
        • Steere A.C.
        • Sikand V.K.
        • Meurice F.
        • Parenti D.L.
        • Fikrig E.
        • Schoen R.T.
        • et al.
        Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group.
        N Engl J Med. 1998; 339: 209-215
        • Plotkin S.A.
        Need for a new Lyme disease vaccine.
        N Engl J Med. 2016; 375: 911-913
        • Livey I.
        • O'Rourke M.
        • Traweger A.
        • Savidis-Dacho H.
        • Crowe B.A.
        • Barrett P.N.
        • et al.
        A new approach to a Lyme disease vaccine.
        Clin Infect Dis. 2011; 52: s266-s270
        • Comstedt P.
        • Hanner M.
        • Schüler W.
        • Meinke A.
        • Lundberg U.
        Design and development of a novel vaccine for protection against Lyme borreliosis.
        PLoS One. 2014; 9e113294
        • Comstedt P.
        • Schüler W.
        • Meinke A.
        • Lundberg U.
        The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes.
        PLoS One. 2017; 12e0184357
        • Koide S.
        • Yang X.
        • Huang X.
        • Dunn J.J.
        • Luft B.J.
        Structure-based design of a second-generation Lyme disease vaccine based on a C-terminal fragment of Borrelia burgdorferi OspA.
        J Mol Biol. 2005; 350: 290-299
        • Earnhart C.G.
        • Marconi R.T.
        An octavalent Lyme disease vaccine induces antibodies that recognize all incorporated OspC type-specific sequences.
        Hum Vaccin. 2007; 3: 281-289
        • Niesobecki S.
        • Hansen A.
        • Rutz H.
        • Mehta S.
        • Feldman K.
        • Meek J.
        • et al.
        Knowledge, attitudes, and behaviors regarding tick-borne disease prevention in endemic areas.
        Ticks Tick Borne Dis. 2019; 10: 101264
        • Daltroy L.H.
        • Phillips C.
        • Lew R.
        • Wright E.
        • Shadick N.A.
        • Liang M.H.
        A controlled trial of a novel primary prevention program for Lyme disease and other tick-borne illnesses.
        Health Educ Behav. 2007; 34: 531-542
        • Apanaskevich D.A.
        • Oliver Jr., J.R.
        Life cycles and natural history of ticks.
        in: Sonenshine D.E. Roe R.M. Biology of Ticks. 2nd ed. Oxford University Press, New York, NY2014: 59-73
        • Nadelman R.B.
        Erythema migrans.
        Infect Dis Clin North Am. 2015; 29: 211-239
        • Dennison R.
        • Novak C.
        • Rebman A.
        • Venkatesan A.
        • Aucott J.
        Lyme disease with erythema migrans and seventh nerve palsy in an African-American man.
        Cureus. 2019; 11e6509
        • Biggs H.M.
        • Behravesh C.B.
        • Bradley K.K.
        • Dahlgren F.S.
        • Drexler N.A.
        • Dumler J.S.
        • et al.
        Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis—United States.
        MMWR Recomm Rep. 2016; 65: 1-44