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Tick Talk: Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry & Biophysics Osher Mini Med School, 11/14/19

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Page 1: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Tick Talk: Advancing the Understanding and Prevention

of Tick-borne Diseases

Seemay ChouUCSF Dept of Biochemistry & Biophysics

Osher Mini Med School, 11/14/19

Page 2: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Malaria Sleeping sickness Lyme disease

Page 3: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Topics:1. Ticks and their vector capacity

2. Challenges associated with diagnosing Lyme

3. Strategies for blocking tick-borne diseases

4. What else can we learn from ticks?

Page 4: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Ixodes scapularisIxodes pacificus

Dermacentor andersoniDermacentor variablis

Amblyomma maculatumAmblyomma americanum

EhrlichiosisRickettsiosis

Mammalian Meat Allergy

Lyme DiseaseAnaplasmosis

BabesiosisPowassan Disease

Rocky Mountain Spotted FeverColorado Tick Fever

Ticks are vectors for human diseases

Page 5: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Different ticks have different lifestyles

Hard

Ixodes scapularis

scutumcapitulum

Soft

Ornithodoros savignyi

Page 6: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Different ticks have different lifestyles

Hard

Ixodes scapularis

• 3 stages: larvae, nymphs, adults• Single bloodmeal between each• Bloodmeal: days to over a week

Page 7: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Borrelia burgdorferi Lyme diseaseIxodes scapularis

Centers for Disease Control

Cases have tripled in past decade

Most commonly reported vector-borne disease in U.S.

Lyme disease cases in the U.S. are on the rise

Page 8: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Tick–pathogen relationships are remarkably specific

Source: CDC.gov

Page 9: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Lyme disease is restricted to where tick vectors are

Source: CDC.gov

Page 10: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

West coast vector: Ixodes pacificus

Western blacklegged tick

Page 11: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

West coast vector: Ixodes pacificus

Sceloporus occidentalisWestern fence lizard

Page 12: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry
Page 13: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

County level distribution of submitted Ixodes

Nieto et al, 2018

Page 14: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Distribution of other tick species received

Nieto et al, 2018

Page 15: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

All submissions(4261)

Ixodes scapularis(2574, 60%)

Questing/biting ticks collected from humans in NE

Dermacentor variablis 33%; Amblyomma americanum 2%Porter et al, 2019

Page 16: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Submissions varied by species, stage, seasonN

umb

er o

f tic

ks re

ceiv

ed/w

eek

Porter et al, 2019

Page 17: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

0

50

100

150

200

250

300

350

400

450

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar

Ixodes species also had different collection patterns

Ixodes scapularisIxodes pacificus

Courtesy of Wendy Adams, Nate Nieto

Page 18: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Vector capacity = ecology + competence

Vector competenceIntrinsic ability to acquire, carry, and transmit microbes.

Page 19: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

B. burgdorferi transmission cycle

Reviewed in Sonenshine, D. Biology of Ticks, 2014 ed.

Adults

Nymphs

Larvae

Acquisition

Page 20: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Topics:1. Ticks and their vector capacity

2. Challenges associated with diagnosing Lyme

3. Strategies for blocking tick-borne diseases

4. What else can we learn from ticks?

Page 21: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Borrelia burgdorferi

Lyme disease is difficult to diagnose/treat

Arthritis, fatigue, neurodegeneration

Incubation period: 3-32 days

Limited window for treatment

Difficult to detect in blood

Unsuccessful vaccine (2002)

Page 22: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Ticks can carry multiple pathogens

Nationwide

Borrelia burgdorferi sl 6.14%Borrelia miyamotoi 0.91%

A. phagocytophilum 1.76%

Babesia microti 0.66%

*Ehrlichia and Rickettsia spp., high prevalence in some places (~40%)

CoinfectionsBb + Bm (N = 11)Bb + Ap (N = 14)Bb + Bab (N = 8)

Bm + Ap (N = 1)Bm + Bab (N = 2)

Ap + Bab (N = 1)

Tri-infectionBb + Bm + Bab (N = 3)

New York and PennsylvaniaBb + Ap + Bab (N = 1)

Minnesota

Courtesy of Wendy Adams, Nate Nieto

Page 23: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Topics:1. Ticks and their vector capacity

2. Challenges associated with diagnosing Lyme

3. Strategies for blocking tick-borne diseases

4. What else can we learn from ticks?

Page 24: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Nature Medicine, 2014

Page 25: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Paratransgenesis to control vectors

A. aegypti mosquitoes transmit Zika virus(also dengue, chikungunya, yellow fever)

Infect with bacterium Wolbachia

Aedes aegypti

Page 26: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

The Lyme pathogen is in gut of I. scapularis ticks

mg = midgut

ov = ovary

Ross B et al, ISME (2018)

Page 27: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Some ticks have other kinds of bacteria

Negatively correlates with B. burgdorferi

Ross B et al, ISME (2018)

Page 28: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry
Page 29: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Topics:1. Ticks and their vector capacity

2. Challenges associated with diagnosing Lyme

3. Strategies for blocking tick-borne diseases

4. What else can we learn from ticks?

Page 30: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Ticks are master regulators of us (their food)

Page 31: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Both ticks and pathogens rely on saliva

Pool feeders

Prolonged bloodmeals

90% of fluid is secreted

Saliva-activated transmission

Page 32: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Adventures in collecting tick spit

~102 proteins in sialomeComposition changes over timeArthropod saliva is protease-rich

Page 33: Tick Talk: Advancing the Understanding and Prevention of Tick … · 2019-11-21 · Advancing the Understanding and Prevention of Tick-borne Diseases Seemay Chou UCSF Dept of Biochemistry

Questions?