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Lyme Disease and Its Epidemiology
Diane E. Griffin, MD, PhD
Johns Hopkins University
Diane E. Griffin, MD, PhD
Professor and Chair, Department of Molecular
Microbiology and Immunology
Research interests fall in the area of pathogenesis of viral
diseases, with a particular focus on measles and
alphavirus encephalitis
Editor for Field’s Virology
President-elect, American Society for Microbiology
3
Section A
Background/History
First Recognition of Lyme Arthritis in Connecticut, 1976
5
Characteristics of the First 52 Cases Identified
6
Prevalence of Lyme Arthritis on Four Roads in Connecticut
Affected/total
Prevalence per
100 children
Old Lyme
Road A
Road B
4/51
4/65
7.8
7.7
East Haddam
Road C
Road D
4/26
5/33
15.4
12.1
17/175
9.7
Site
Total
7
Lyme Arthritis: Associated Symptoms (12 Patients)
Malaise
Chills and fever
Headache
Stiff neck
Backache
Myalgias
Nausea and vomiting
Sore throat
75%
75%
50%
50%
33%
25%
25%
8%
Source: Steere, A. C., et al. (1977, June). Ann Intern Med, 86(6), 685–698.
8
Typical Lyme Arthritis
Photo by Dr. Alan Steere, Massachusetts General Hospital, Boston.
9
Typical Skin Lesion: Erythema Migrans (EM)
Source: CDC
10
Secondary Lyme Disease: Cardiac Manifestations
Atrioventricular block
Primary
Wenckebach
Complete
90%
40%
30%
T wave inversion
50%
11
Bell’s Palsy Due to Lyme Disease
Source: CDC
12
Secondary Lyme Disease: Neurologic Manifestations
Meningitis
Encephalitis
Cranial neuropathy
Radiculitis
80%
40%
50%
25%
13
Time Course of Various Lyme Disease Clinical Syndromes
14
Case-Control Study
Lyme disease patients and neighbors, 1977
Patients
Neighbors
P
Male
53
44
Rural environment
47
45
Woods activities
77
61
Pets
86
81
Pet cats
63
39
<0.01
Ticks on pets
70
27
<0.0001
Farm animals
26
11
<0.05
Tick bites
44
26
<0.05
Mosquito bites
72
70
Source: Steere, A. C., Broderick, T. F., and Malawista, S. E. (1978, October). Am J Epidemiol, 108(4), 312–321.
15
Seasonal Incidence of Lyme Disease in the U.S.
16
Disease Transmission
17
Lyme Disease: Attack Rates on Each Side of River, 1977
Rate per 1,000 residents
East side of Connecticut River
2.8
West side of Connecticut River
0.1
Source: Steere et al. (1978). Am J Epidemiol, 108, 312.
18
Ticks Found on Each Side of the Connecticut River
West
East
l. scapularis
D. variabilis
l. scapularis
D. variabilis
Humans
8
37
33
20
Dogs
2
78
27
95
Cats
12
17
3
5
White-footed mice
29
26
498
143
Voles
0
5
3
2
Chipmunks
3
0
2
0
Raccoons
0
10
3
69
Skunks
0
0
1
6
Dragging
0
0
8
43
Total
54
173
578
373
19
Section B
Identification of the Etiologic Agent of Lyme Disease and Its
Distribution
Willy Burgdorfer, PhD
Medical entomologist
Rocky Mountain Laboratories
Bitterroot Mountains, Montana
21
Where Burgdorfer Studied Ticks in the Summer of 1981
22
Spirochetes Seen in the Midgut of Deer Ticks
Spirochetes seen in the midgut of deer ticks collected on
Shelter Island
From Burgdorfer W, et al. Lyme disease-a tick-borne spirochetosis? Science, 1982;216:1317. Reprinted with
permission from AAAS. All rights reserved.
23
Isolation of B. burgdorferi from Patients with Lyme Disease
Titers of antibody against spirochetes isolated from three
patients
IgM titer
Source
IgG titer
Days sick
Culture
2 weeks
Culture
2 weeks
Blood
2
16
64
16
512
Skin
25
64
32
32
128
Spinal fluid
70
32
32
512
1024
Source: Steere et al. (1983). N Engl J Med, 308, 733.
24
Distribution of Erythema Migrans Cases in Europe
25
Distribution of Ixodes ricinus in Europe
ricinus
26
Manifestations Differ in Europe and the U.S.
Distribution of manifestations of Lyme disease in 1,471 patients in Southern Sweden*
Manifestation
Erythema
migrans
Neuroborreliosis
Arthritis
Acrodermatitis
Lymphocytoma
Carditis
Erythema
migrans
1,075
40
10
1
9
1
Neuroborreliosis
40
176
8
2
3
1
Arthritis
10
8
65
8
1
0
Acrodermatitis
1
2
8
34
0
0
Lymphocytoma
9
3
1
0
26
0
Carditis
1
1
0
0
0
5
≥ 3 manifestations
3
5
6
2
2
0
Total no. (%)
1,139 (77)
235 (16)
98 (7)
47 (3)
41 (3)
7 (<1)
*The numbers of cases with only one manifestation of disease are indicated in boldface
type. Six patients had three or more manifestations, and their data are presented on a
separate line.
Source: Berglund et al. (1995). N Engl J Med, 333, 1319.
27
Borrelia burgdorferi Species
Borrelia burgdorferi species
B. burgdorferi sensu lato
B. burgdorferi sensu stricto
B. afzelii
B. garinii
28
Lyme Neuroborreliosis
Summarized differences in neurologic manifestations of
Lyme disease
Source: Pachner et al. (2004, September). Ann Neurol, 56(3), 361–370.
29
Lyme Disease Incidence in the U.S.
30
Lyme Disease: Reported Cases by County, U.S., 2001
Source: CDC.
31
Annual Incidence of Reported Cases, by Age and Sex
Source: CDC.
32
Section C
Natural Cycle and Reservoir of the Organism
Ixodes scapularis Ticks
Female
Nymph
Male
Source: CDC.
34
Abundance of Different Stages by Time of Year
Abundance of different
stages of Ixodes ticks
at different times of year
35
Hosts for Ixodes scapularis
White-tailed deer
Photo by martytdx. Some rights reserved.
White-footed mouse
Photo by Chili Bob. Some rights reserved.
36
Tick Cycle in Relation to B. burgdorferi Transmission
37
Changes in North American Wildlife Populations
Species
1935*
1985
Bison
12,800
65,000
60
6,
North American Elk
225,000
500,000
Pronghorn Antelope
40,000
750,000
Trumpeter Swan
73
10,000
White-tailed Deer
5 million
14.7 million
Whooping Crane
29
138
31,250
2.5 million
California Condor
Wild Turkey
*Estimates by US Fish and Wildlife Service
38
Percent Ixodes Ticks Positive for B. burgdorferi, by Location
Shelter Island, New York
Southeast Connecticut
Northern California
Source: Burgdorfer et al. (1985). Am J Trop Med Hyg, 34(5), 925–930.
Up to 100%
35%
1–2%
39
Distribution of Ixodes scapularis and Ixodes pacificus
40
Maintenance of the Natural Cycle: East and West
Maintenance of the natural cycle is different in the eastern & western U.S.
41
National Lyme Disease Risk Map
Source: CDC
42
Effect of Duration of Attachment
Transmission of B. burgdorferi by nymphal ticks—effect of
duration of attachment
Hours of
attachment
No. of infected
ticks fed
Mice infected/total
36
14.4 ± 3.5
1/14
42
16.4 ± 4.7
3/12
48
13.0 ± 3.7
6/8
Conclusion: Ticks must remain attached for about 48 hours to transmit infection
43
Efficacy of OspA Lyme Disease Vaccine in Two Trials
Efficacy of OspA Lyme Disease Vaccine in 2 Trials
Study and Year
Placebo group
# subjects (cases)
Vaccine group
# subjects (cases)
Measured
Vaccine Efficacy
(95% CI)
End of year 1
Sigal et al
Steere et al
Definite/probable
5149 (37)
5156 (12)
68 (36-85)
5467 (43/13)
5469 (22/2)
49 (15-69)/
83 (32-97)
1411 (5)
3770 (26)
1379 (2)
3745 (22)
0 (0-60)
92 (69-97)
5469 (16/0)
76 (58-86)/
100 (26-100)
End of year 2
Sigal et al
2 doses
3 doses
Steere et al
3 doses (def/prob) 5467 (66/15)
44
Borrelia Osp
Expression of outer surface proteins (Osp) on Borrelia in
the midgut of unfed ticks
Osp A
Osp C
Figure Source: Schwan TG, et al. Induction of an outer surface protein on Borrelia burgdorferi
during tick feeding. PNAS 1995;92:2909-13. Copyright (1995) National Academy of Sciences,
45
U.S.A
How the Osp A Lyme Disease Vaccine Protects
46
Lyme Disease Prevention
Distribution of pyrethrin-impregnated cotton balls in
habitat of white-footed mice
− Kills ticks overwintering with mice
47
Lyme Disease Prevention
Treatment
Ticks infected
Persons with LD
Placebo
23/159 (14%)
2/173 (1.2%)
Amoxicillin
30/185 (16%)
0/192 (0%)
Source: Shapiro et al. (1992). N Engl J Med, 327, 1769.
48
Conclusions
Lyme disease is caused by a spirochetal bacteria,
Borrelia burgdorferi
The reservoir host in the eastern U.S. is the white-footed
mouse
Borrelia is maintained in a geographically restricted
natural cycle between ticks and mammals
Human disease is determined by
− Exposure to infected ticks
− The species of Borrelia causing infection
49
