Tick-borne viral diseases in
the United States
J. Erin Staples
Arboviral Diseases Branch
Centers for Disease Control and Prevention
Fort Collins, CO
March 31, 2015
National Center for Emerging and Zoonotic Infectious Diseases
Division of Vector-borne Diseases
Disclosure
The Association of Public Health Laboratories adheres to established standards
regarding industry support of continuing education for healthcare professionals.
The following disclosures of personal financial relationships with commercial
interests within the last 12 months as relative to this presentation have been
made by the speaker(s):
J. Erin Staples, MD, PhD - Nothing to disclose.
2
Objectives

Describe geographic distribution and clinical
features of tick-borne viral diseases

Understand role of molecular and serologic
diagnostic testing in confirming tick-borne viral
infections
3
Colorado tick fever
4
Colorado tick fever (CTF) virus

Double-stranded RNA virus

Family: Reoviridae; Genus: Coltivirus

Transmitted primarily by Dermacentor andersoni
(Rocky Mountain wood tick)

Small rodents are primary reservoir
5
Ecology of CTF virus
6
CTF epidemiology

Endemic to mountainous regions (elevation of
4,000-10,000 feet) of western U.S. and
southwestern Canada

CTF is currently reportable in six states
 Arizona, Colorado, Montana, Oregon, Utah, and
Wyoming

Up to 90% of cases recall tick exposure

Blood-borne and laboratory transmission rare
7
Approximate geographic distribution of
Dermacentor andersoni and counties of residence
for CTF cases, United States – 2002-2012
* All cases were acquired in states where local transmission of CTF virus has been reported previously.
**Derived from James AM, Freier JE, Keirans JE, Durden LA, et al. Distribution, seasonality, and hosts of the Rocky Mountain
wood tick in the United States. J Med Entomol 2006; 43:17–24.
8
Number of CTF cases by year, United
States – 1987-2012
Median 55 cases/year
Median 5 cases/year
120
Number of cases
100
80
60
40
20
0
9
Month of illness onset for CTF cases, United
States – 2002-2012
30
Number of cases
25
20
15
10
5
0
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Month of illness onset
10
Demographics of CTF cases,
United States – 2002-2012
Characteristic
N=75
n (%)
Sex
Male
Age (years)
0-19
20-39
40-59
≥60
Unknown
47 (63)
11
13
30
19
2
(15)
(17)
(40)
(25)
(3)
11
Clinical features of CTF

Incubation period 2-3 days (range 1-14 days)

Sudden onset of fever; can be bi-phasic

Other symptoms include chills, headache,
myalgia, and malaise

Rare reports of meningitis, encephalitis,
hepatitis, pericarditis, pneumonia, coma

15-30% of cases hospitalized
12
Clinical laboratory findings of CTF

Some findings secondary to CTF virus infecting
hematopoietic progenitor cells

Leukopenia with relative lymphocytosis

Atypical lymphocytes

Moderate thrombocytopenia
13
Treatment and outcome for CTF

No specific treatment; supportive therapy

Illness duration 7-10 days but malaise can last
for weeks

Death is rare
14
Diagnostic testing for CTF virus infection

Testing is available at Focus Diagnostics,
Montana Public Health Laboratory, and CDC

CTFV infects red blood cells; leads to prolonged
viremia and delayed antibody production

RT-PCR is most sensitive for acute samples;
also can culture virus

IFA or neutralization testing for antibodies may
not be positive until 2-3 weeks post infection

IHC also available for tissues
15
Number and proportion of samples positive
for CTF virus infection by days post onset
and assay
Days post
illness onset
0-6
RNA
No. pos/
No. tested (%)
14/14 (100)
Neutralizing
antibodies
No. pos/
(%)
No. tested
0/12 (0)
IgG antibodies
No. pos/
(%)
No. tested
1/8 (13)
7-13
8/8 (100)
1/2 (50)
1/2 (50)
14-20
1/1 (100)
2/4 (50)
5/6 (83)
≥21
0/0 (0)
16/16 (100)
3/3 (100)
16
Summary of CTF virus and disease

Likely under-recognized cause of febrile illness
in spring and early summer in Western U.S.

Majority of cases recall tick exposure

Samples collected in first 14 days of illness
should be tested for viral RNA

Antibody testing not reliably positive until 3
weeks after illness onset

Defer blood donors for 6 months
17
References for CTF








Yendell SJ, Fischer M, Staples JE. Colorado tick fever in the United States, 20022012. Vector Borne Zoonotic Dis 2015; in press.
Brackney MM, Marfin AA, Staples JE, et al. Epidemiology of Colorado tick fever in
Montana, Utah, and Wyoming, 1995-2003. Vector Borne Zoonotic Dis 2010;10:381-5.
Eisen L, Ibarra-Juarez LA, Eisen RJ, Piesman J. Indicators for elevated risk of human
exposure to host-seeking adults of the Rocky Mountain wood tick (Dermacentor
andersoni) in Colorado. J Vector Ecol 2008;33:117-28.
CDC. Transmission of Colorado tick fever virus by blood transfusion -- Montana.
Morb Mortal Wkly Rep 1975;24:422-7.
Romero JR, Simonsen KA. Powassan encephalitis and Colorado tick fever. Infect Dis
Clin North Am 2008;22:545-59.
Lambert AJ, Kosoy O, Velez JO, Russell BJ, Lanciotti RS. Detection of Colorado tick
fever viral RNA in acute human serum samples by a quantitative real-time RT-PCR
assay. J Virol Methods 2007;140:43-8.
Marfin A, Campbell G. Colorado tick fever and related Coltivirus infections. In:
Goodman J, ed. Tick-Borne Diseases of Humans. Washington, D.C.: ASM Press;
2005:143-9.
Attoui H, Jaafar FM, de Micco P, de Lamballerie X. Coltiviruses and Seadornaviruses
in North America, Europe, and Asia. Emerging Infectious Diseases 2005;11:1673-9.
18
Powassan (POW) virus

Single-stranded RNA virus with two lineages
 POW virus or Lineage I POW virus
 Deer tick virus (DTV) or Lineage II POW virus

Family: Flaviviridae; Genus: Flavivirus
 Member of tick-borne encephalitis group

Transmitted primarily by Ixodes spp.
 Lineage I: I. cookei, I. marxi, and I. spinipalpus
 Lineage II: I. scapularis, I. dammini; D. andersoni

Small to medium mammals (rodent, woodchucks,
skunks) are main reservoirs
19
POW virus disease epidemiology

Endemic primarily in northeastern states and
Great Lake region

POWV disease is nationally notifiable

No other modes of transmission documented
 Theoretical risk for blood and in utero transmission
 Tick-borne encephalitis virus transmitted via ingestion
of milk from infected ungulates
20
Geographic distribution of POW virus
neuroinvasive disease cases,
United States – 2004-2013
21
Number of POW virus disease cases by
year, United States – 1970-2013
Median 0 cases;
Northeast US
18
Median 6 cases;
NE and North
Central US
Number of cases
16
14
12
10
8
6
4
2
0
Year
22
Month of illness onset for POW virus
disease cases, United States – 2004-2013
20
18
Number of cases
16
14
12
10
8
6
4
2
0
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Month of illness onset
23
Demographics of POW virus disease cases,
United States – 2004-2013
Characteristic
N=65
n (%)
Sex
Male
Age (years)
0-19
20-39
40-59
≥60
48 (74)
10
8
15
32
(15)
(12)
(23)
(49)
24
Clinical features of POW virus disease

Incubation period range 8-34 days

Asymptomatic or mild disease may occur

Fever, headache, vomiting, and weakness are
initial symptoms of neuroinvasive disease

Progresses to altered mental status, aphasia,
paresis, movement disorders, nerve palsies

88% of cases hospitalized
25
Clinical laboratory and imaging findings of
POW virus disease

CSF with lymphocyte pleocytosis though
neutrophils can predominate early

Normal or mildly elevated CSF protein

Normal CSF glucose

Brain MRI with demyelinating disease or microvascular ischemia in parietal or temporal lobes
26
Treatment and outcome for
POW virus disease

No specific treatment; supportive therapy

Roughly half of cases have long-term neurologic
sequelae

10-20% of cases are fatal
27
Diagnostic testing for POW virus infections

Testing is available at Minnesota and New York
state public health laboratories and CDC

Viremia rarely detected early in illness and usually
only with nested RT-PCR

Antibody measured by IgM and IgG EIA and
neutralization testing
 Cross-reactivity can occur in EIA with related flaviviruses
 Antibody testing can not differentiate between lineages

IHC also available for tissues
28
Summary of POW virus and disease

Likely under-recognized cause of neuroinvasive
disease during tick season

Occurs predominantly in northeastern and north
central United States

Neutralizing antibody testing needed to confirm
diagnosis due to flavivirus cross-reactivity
29
References for POWV








Lindsey NP, Lehman JA, Staples JE, Fischer M. West Nile virus and other arboviral
diseases -- United States, 2013. MMWR 2014;63(24):521-526.
Dupuis AP, Peters RJ, Pruinski MA et al. Isolation of deer tick virus (Powassan virus,
lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts
sampled in the Hudson Valley, New York State. Parasites & Vectors. 2013;6:185.
Brackney DE, Nofchissey RA, Fitzpatrick KA, Brown IK, Ebel GD. Stable prevalence
of Powassan virus in Ixodes scapularis in a northern Wisconsin focus. Am J Trop Med
Hyg. 2008;79(6):971-973.
Ebel GD. Update on Powassan virus: emergence of a North American tick-borne
flavivirus. Annu Rev Entomol. 2010;55:95-110.
Ebel GD, Spielman A, Telford SR, 3rd. Phylogeny of North American Powassan virus.
J Gen Virol. Jul 2001;82(Pt 7):1657-1665.
Hinten SR, Beckett GA, Gensheimer KF, et al. Increased recognition of Powassan
encephalitis in the United States, 1999-2005. Vector Borne Zoonotic Dis.
2008;8(6):733-740.
Johnson DK, Staples JE, Sotir MJ, Warshauer DM, Davis JP. Tickborne Powassan
virus infections among Wisconsin residents. Wis Med J. 2010;109(2):91-7.
Tavakoli NP, Wang H, Dupuis M, et al. Fatal case of deer tick virus encephalitis. N
Engl J Med. 2009;360(20):2099-2107.
30
Initial Heartland virus disease cases

In June 2009, two adult males seen at hospitals
in northwestern Missouri

Both relatively healthy; one reported recent
diagnosis of Type II diabetes mellitus

Symptoms and signs were similar for both
 Fever, fatigue, anorexia, and diarrhea
 Leukopenia and thrombocytopenia
31
Exposures for initial cases

Both farmers who resided and worked land

Both reported multiple tick exposures prior to
their illness onset

No recent travel, vaccinations, or other recent
illnesses
32
Hospital course for initial cases

Both were admitted and received doxycycline for
presumptive ehrlichiosis

Failed to improve and laboratory parameters
worsened during hospitalization
 Thrombocytopenia became more significant
 Moderately elevated liver transaminases developed

Both patients discharged home after 10-12 days

Laboratory testing for etiology was negative
33
Identification of novel virus

Acute samples were sent to CDC to culture for
Ehrlichia chaffeensis

Both showed cytopathic effects
 Characteristic morulae were not seen

Electron microscopy performed
identified bunyavirus-like particles

In 2011, next generation sequencing identified
virus as novel phlebovirus, Heartland virus
34
Entomologic evaluation

Ticks and mosquitoes collected from farmers’
residences and local areas to test for HRTV

Heartland virus recovered in 10 Amblyomma
americanum (Lone star tick) pools

Amblyomma americanum likely vector
35
Identification of additional Heartland virus
disease cases

Epidemiologic investigation implemented with
MO Dept of Health and Senior Services in 2012

Prospect study with participants enrolled in 7
medical facilities throughout MO

Enrollment criteria includes fever, leukopenia,
and thromobocytopenia
 Excludes non-infectious etiologies

In 2013, cases tested from other locations
36
Epidemiology of Heartland virus
disease cases

From 2012-2013, 6 additional cases identified
from Missouri and Tennessee

All patients were males

Median age is 58 years (range: 50-80 years)

Illness onset was in May (n=3), July (1), and
September (2)
37
Clinical features and outcome of Heartland
virus disease

Of 5 patients where symptoms were collected,
all reported fatigue and anorexia

Other symptoms included headache, nausea,
myalgia, or arthralgia

Four (67%) of 6 patients were hospitalized

One (17%) died
38
Reported exposures for Heartland virus
disease cases (N=6)

All patients reported spending >1 hour per day
outside

5 (83%) reported tick bites in 14 days prior to
illness onset
39
Diagnostics testing for
Heartland virus infections

Testing currently available at CDC; several
academic centers performing RT-PCR

RT-PCR on acute serum is often positive for
Heartland viral RNA

Neutralization test used for determining antibody
titers in acute and convalescent samples

IgM MIA and IFA and IgG MIA and ELISA have
been developed but need further validation

IHC available to test tissues
40
Summary of Heartland virus and disease

Previously unrecognized human pathogen, likely
transmitted by A. americanum

Clinically similar to ehrlichiosis/anaplasmosis

Consider diagnosis in patients with fever,
leukopenia, and thrombocytopenia who test
negative for tick-borne pathogen or do not
improve on doxycycline

Serologic and molecular testing can be used to
diagnosis Heartland virus infections
41
References for Heartland virus

McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe
febrile illness in Missouri. N Engl J Med 2012;367:834-841.

Savage HM, Godsey MS Jr, Lambert A, et al. First detection of heartland virus
(Bunyaviridae: Phlebovirus) from field collected arthropods. Am J Trop Med Hyg
2013;89:445-452.

Pastula DM, Turabelidze G, Yates KF, et al. Notes from the field: Heartland virus
disease - United States, 2012-2013. Morb Mortal Wkly Rep 2014;63:270-271.

Muehlenbachs A, Fata CR, Lambert AJ, et al. Heartland virus-associated death in
Tennessee. Clin Infect Dis 2014;59:845-850.
42
Prevention of tick-borne viral diseases

No vaccines to prevent tick-borne viral diseases
in United States

Tick-borne encephalitis vaccine available in
Canada and Europe

Avoid tick bites




Use insect repellent
Wear long sleeves and pants
Avoided wooded or bushy areas with high grass
Perform thorough tick checks after spending time
outdoors to remove ticks before they attach
43
CDC websites and downloadable
information on tick-borne diseases

Colorado tick fever
 http://www.cdc.gov/coloradotickfever/

Powassan virus disease
 http://www.cdc.gov/powassan/

Heartland virus disease
 http://www.cdc.gov/ncezid/dvbd/heartland/index.html

General tick-borne disease information
 http://www.cdc.gov/ticks/index.html

Tickborne Diseases of the United States: A Reference
Manual for Health Care Providers, Second Edition
 http://www.cdc.gov/lyme/resources/TickborneDiseases.pdf
 Free app in Apple App store (“cdc tickborne”); android version
anticipated by May 2015
44
Questions
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: [email protected] Web: http://www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of
the Centers for Disease Control and Prevention.
National Center for Emerging and Zoonotic Infectious Diseases
Division of Vector-borne Diseases