Lyme Disease/Lyme Disease/Lyme BorreliosisLyme Borreliosis

By Simone By Simone SwanepoelSwanepoel

OutlineOutline Taxonomy/ History / Life cycleTaxonomy/ History / Life cycle

Morphology of agents involved/ Epidemiology &Morphology of agents involved/ Epidemiology &DistributionDistribution

Ecology / Evolution / Genetics / Physiology/ImmunologyEcology / Evolution / Genetics / Physiology/Immunology

Parasite/host relationshipsParasite/host relationships

Symptoms/ Treatment/ PreventionSymptoms/ Treatment/ Prevention

Future ResearchFuture Research

IntroductionIntroduction

Leading arthropod-associated disease in theLeading arthropod-associated disease in theUSAUSA

24, 000 human cases reported in USA (~10 % of24, 000 human cases reported in USA (~10 % ofphysician diagnosed cases)physician diagnosed cases)

12 states 12 states –– 95 % of cases (CDC 2005) 95 % of cases (CDC 2005) Greatest incidence~Children under 14 & adultsGreatest incidence~Children under 14 & adults

over 40over 40 Summer Months ( Morshed et al. 2005)Summer Months ( Morshed et al. 2005) Multisystem disorderMultisystem disorder Great imitator ~ myriad of symptomsGreat imitator ~ myriad of symptoms

TaxonomyTaxonomy Pathogen/CausativePathogen/Causative

agent of disease ~agent of disease ~ Gram-negative Gram-negative

spirochetal bacteriaspirochetal bacteria(Barbour 1984)(Barbour 1984) Borellia burgdorferiBorellia burgdorferi

Principal vectorPrincipal vector ~ ~ - Ixodes scapularis - Ixodes scapularis

(blacklegged tick/(blacklegged tick/‘‘deerdeer’’ tick/hard tick) tick/hard tick) & &Ixodes PacificusIxodes Pacificus(Padgett and Lane(Padgett and Lane2001)2001)

Figure1. B.burgdorferi bacteria (CDC)Figure 2. Larva, nymph, male and female I.scapularis (CDC).

TaxonomyTaxonomy Principal reservoir ~Principal reservoir ~ (nymphs) (nymphs)

-White footed mouse-White footed mouse- - Peromyscus leucopusPeromyscus leucopus

Principal host ~Principal host ~(adults)(adults)

-White-tailed deer, -Odocoileus

virginianus

Figure 4. O. virginianus deer (CDC).Figure3.P.leucopusmouse.

Life CycleLife Cycle

Figure5.Two‐yearLifeCycleforI.scapularis(CDC)

Life CycleLife Cycle

Figure 6. Seasonal activity of I. scapularis larvae, nymphs, and adults(CDC).

Figure 5. The enzootic cycle of B. burgdorferi infection in the northeasternUS and intersection with human Lyme disease (Journal of ClinicalInvestigation 2004.)

Natural HistoryNatural History 1764 - Reverend Dr John Walker1764 - Reverend Dr John Walker

1975 - Disease first recognized as a1975 - Disease first recognized as aclinical entity clinical entity –– Lyme, Connecticut (WHO) Lyme, Connecticut (WHO)

1981 - Causative bacteria discovered - Dr.1981 - Causative bacteria discovered - Dr.Willy BurgdorferiWilly Burgdorferi –– Long Island, New York.Long Island, New York.

Extensive History in Europe Extensive History in Europe –– 20 20thth Century Century

Morphology of Morphology of IxodidaeIxodidae

Figure 7. Hypothetical Male and Female Ixodidae (hard ticks) with keycharacteristics labeled (CDC).

Tick BitesTick Bites

Figure 8. Scanning electron micrographs of the mouthparts of the blacklegged tick (CDC)

EpidemiologyEpidemiology

Figure 9. Reported cases of Lyme Disease in USA ~ 2005 (CDC).

DistributionDistributionTick VectorTick Vector

Figure 10. Distribution of the tick species associated with human granulocytic anaplasmosis (HGA), I. scapularis, I.pacificus; and human monocytotropic ehrlichiosis (HME), A. americanum (CDC).

Ecology & EvolutionEcology & Evolution UrbanizationUrbanization Anthropogenic factorsAnthropogenic factors

B.burgdorferi ~ B.burgdorferi ~ highhighstrain diversitystrain diversity

Genetic & PhysiologicalGenetic & PhysiologicalAspectsAspects

Genome Sequencing (Steere et al. 2004).Genome Sequencing (Steere et al. 2004). Spirochetes- Change of OpsA to OpsCSpirochetes- Change of OpsA to OpsC

outer surface protein for mammalianouter surface protein for mammalianinfection.infection.

Spirochete bind mammalian plasminogen.Spirochete bind mammalian plasminogen. Surface protein of Surface protein of B.burgdoferB.burgdoferi - C6i - C6

peptide of the VslE protein antigen-peptide of the VslE protein antigen-immune responseimmune response

ImmunologyImmunology

Figure 12. Host mechanisms of spirochetal killing (Journal of Clinical Investigation 2004).

ParasitismParasitism

Obligate blood-feeders (ticks)Obligate blood-feeders (ticks)

Require animal host to survive &Require animal host to survive &reproducereproduce

Wide host range (people/pets/livestock)Wide host range (people/pets/livestock)

Depends on host for nutritionalDepends on host for nutritionalrequirementsrequirements

Clinical signs & symptomsClinical signs & symptoms Early localized/Early localized/

disseminateddisseminatedinfectioninfection CharacteristicCharacteristic

Erythema MigransErythema Migransrash (EM rash)/ bulls-rash (EM rash)/ bulls-eye rasheye rash

Flu-like SymptomsFlu-like Symptoms Acute neurological/Acute neurological/ cardiac/ ocular cardiac/ ocular

symptomssymptoms

Late persistentLate persistentinfectioninfection

Myriad of chronicMyriad of chronicdisabling symptomsdisabling symptoms

Brain & nervesBrain & nerves(neurological(neurologicalsymptoms), eyes,symptoms), eyes,joints (arthritis) andjoints (arthritis) andheart.heart.

Figure 11. Characteristic bulls-eye rash

Diagnosis & Treatment ofDiagnosis & Treatment ofDisease/SymptomsDisease/Symptoms

EM rashEM rash Difficult to diagnoseDifficult to diagnose Over/underOver/under

diagnoseddiagnosed Blood test Blood test ––

antibodiesantibodies ELISAELISA Western ImmunoblotWestern Immunoblot (Assous et al. 1993) (Assous et al. 1993) False positive/False positive/

negative (PCR)negative (PCR) Techniques improvingTechniques improving

Antibiotics ~Antibiotics ~(including(includingtetracyclines/ mosttetracyclines/ mostpenicillins, and manypenicillins, and manysecond- and third-second- and third-generationgenerationcephalosporins).cephalosporins).

Early treatmentEarly treatment

Figure 12 . An algorithm for the diagnosis and treatment of the early eventssurrounding Lyme disease in the summer months. Serologic testing for Lymedisease has limited utility during the first 1 or 2 weeks of infection, and earlytreatment, without serologic testing, is recommended (Journal of ClinicalInvestigation 2004.)

PreventionPrevention Pesticides (acaricides) / InsectPesticides (acaricides) / Insect

repellantrepellant Create a tick-safe zoneCreate a tick-safe zone Avoid areas with lots of ticksAvoid areas with lots of ticks Keep ticks off skin-Check skinKeep ticks off skin-Check skin

& clothes for ticks& clothes for ticks Biological Control Biological Control ––

landscaping/integrated pestlandscaping/integrated pestmanagement/ decrease deermanagement/ decrease deerpopulationpopulation

Clothing ( light colors &Clothing ( light colors &protective)protective)

Organic approach Organic approach –– Guinea Guineafowlfowl

VaccinationVaccination

Incorporation if recentIncorporation if recentresearchresearch

Chronic Lyme diseaseChronic Lyme disease

Long term treatment in humansLong term treatment in humans

VaccineVaccine

Deer populationDeer population

Future- Lyme diseaseFuture- Lyme disease

Figure 13. Reported cases of Lyme disease in the United States ~ 1991-2005 (CDC).

ConclusionConclusion Taxonomy/ History / Life cycleTaxonomy/ History / Life cycle

Morphology of agents involved/ Epidemiology &Morphology of agents involved/ Epidemiology &DistributionDistribution

Ecology / Evolution / Genetics / Physiology/ ImmunologyEcology / Evolution / Genetics / Physiology/ Immunology

Parasite/host relationshipsParasite/host relationships

Symptoms/ Treatment/ PreventionSymptoms/ Treatment/ Prevention

Future ResearchFuture Research

Works CitedWorks Cited Assous M. V., D.Assous M. V., D. Postic, G.Postic, G. Paul, P.Paul, P. Névot and G.Névot and G. Baranton. 1993.Baranton. 1993.

Western blot analysis of sera from Lyme borreliosis patientsWestern blot analysis of sera from Lyme borreliosis patientsaccording to the genomic species of the according to the genomic species of the BorreliaBorrelia strains used as strains used asantigens. European Journal of Clinical Microbiology & Infectiousantigens. European Journal of Clinical Microbiology & InfectiousDiseases12: 261-268.Diseases12: 261-268.

Barbour A. G. 1984. Isolation and cultivation of Lyme diseaseBarbour A. G. 1984. Isolation and cultivation of Lyme diseasespirochetes. Yale Journal of biology and medicine 57: 521-525.spirochetes. Yale Journal of biology and medicine 57: 521-525.

Center for Disease Control And Prevention. 2009. Learn aboutCenter for Disease Control And Prevention. 2009. Learn aboutLyme Disease. Accessed online atLyme Disease. Accessed online athttp://www.cdc.gov/ncidod/dvbid/lyme/http://www.cdc.gov/ncidod/dvbid/lyme/

Morshed, M. G.,Morshed, M. G., J. D. Scott, K.J. D. Scott, K. Fernando, L. Beati, D. F.Fernando, L. Beati, D. F. Mazerolle,Mazerolle,G. Geddes, and L. A. Durden. 2005. Migratory songbirds disperseG. Geddes, and L. A. Durden. 2005. Migratory songbirds disperseticks across Canada, and first isolation of the ticks across Canada, and first isolation of the LymeLyme diseasediseasespirochete, Borrelia burgdorferi, from the avian tick, Ixodes auritulus.spirochete, Borrelia burgdorferi, from the avian tick, Ixodes auritulus.Journal of Parasitology 91: 780-790.Journal of Parasitology 91: 780-790.

Works CitedWorks Cited PadgettPadgett K. A., and R. S. Lane. 2001. Life Cycle K. A., and R. S. Lane. 2001. Life Cycle

of of Ixodes pacificusIxodes pacificus (Acari: Ixodidae): Timing of (Acari: Ixodidae): Timing ofDevelopmental Processes Under Field andDevelopmental Processes Under Field andLaboratory Conditions. Journal of MedicalLaboratory Conditions. Journal of MedicalEntomology 38:684-693.Entomology 38:684-693.

Steere A. C., J. Coburn and L. Glickstein. 2004.Steere A. C., J. Coburn and L. Glickstein. 2004.The emergence of Lyme disease. Journal ofThe emergence of Lyme disease. Journal ofClinical Investigation 113: 1093-1101.Clinical Investigation 113: 1093-1101.

World Health Organization. 2009. LymeWorld Health Organization. 2009. LymeDisease. Accessed online atDisease. Accessed online athttp://www.who.int/topics/lyme_disease/en/http://www.who.int/topics/lyme_disease/en/