JWeston-assignment-unit 9

PU535 Unit 9 Assignment
PU535 Public Health Biology
Unit 9 Assignment
Julia Weston
Kaplan University

Abstract
Powassan virus is a neuroinvasive disease transmitted by Ixodes spp. ticks that
causes encephalitis and is sometimes fatal. Since its identification in 1958,
there have been less than 100 cases reported in the United States, which has
led to a significant lack of research. Climate change is affecting the
geographical distribution of the virus as the habitats for the ticks expands.
Powassan virus shares a vector with Lyme disease, and as the incidence of
Lyme disease has increased, there has been speculation that an individual
could contract both diseases from one bite. This paper is intended to gather
the current research regarding the seroprevalence, pathophysiology, and
prevention of Powassan virus and to present it in an informative manner.
Introduction
Statement of Problem
Insects such as mosquitoes, ticks, fleas, and flies are a major vector for
disease throughout the world; the World Health Organization (2014) estimates
that more that 17% of infectious diseases are transmitted by these vectors.
Each year, vector-borne (also known as arboviral) diseases cause over 1 million
deaths (WHO, 2014.) Ticks, in particular, spread many different diseases,

including Lyme disease, babesiosis, and Rocky Mountain spotted fever. They
also spread an uncommon virus known as Powassan (POW) virus (CDC, 2015.)
Public health policies have long been aimed at vector control and personal
exposure prevention, which includes protecting pets from tick bites (CDC, 2014.)
Significance of Problem
There is some evidence that the increases in the incidence of tick-borne
diseases like Lyme disease can be attributed to climate change (Brownstein et
al., 2005; Tuite et al., 2013.) Süss et al (2008) suggest that this can occur if
the ticks’ developmental cycle is accelerated, which could cause nymphs to
emerge earlier in the season. Others have postulated that if the populations of
the ticks’ hosts increase, then there will be a commensurate increase in the tick
population (Subak, 2003.) In the context of POW virus, this is significant
because both Lyme disease and POW virus are spread by Ixodes spp. ticks.
POW virus is unique in that it has 2 known lineages that are spread by
different ticks; prototypical POW virus is spread by Ixodes cookei, while deer
tick virus (DTV) is primarily spread by Ixodes scapularis (Ebel, 2010.) Research
has shown that POW virus and DTV cannot be distinguished serologically, and
are effectively the same virus (Ebel, 2010.) While there have been no observed
epidemics of POW virus concurrent with Lyme disease epidemics (Ebel, 2010), it

is not unlikely that the factors that have increased the incidence rate of Lyme
disease could have the same effect on that of POW virus.
Background
POW virus is a tick-borne virus that can cause neuroinvasive disease,
usually presenting as encephalitis, meningoencephalitis, and aseptic meningitis
(Ebel, 2010.) It is a member of the tick-borne encephalitis (TBE) serogroup of
the viral family Flaviviridae (Deardorff et al., 2013) and is the only flavivirus in
North America that is pathogenic in humans (Birge & Sonnesyn, 2012.) It was
first isolated in 1958 from a 5-year-old boy in Powassan, Ontario, Canada, who
died of severe encephalitis (Birge & Sonnesyn, 2012.) Since then, human
infection has been identified in Russia, Siberia, western Canada, and in various
regions of the United States (Lani et al., 2014.) Nearly 60 cases of POW virus
were reported in the United States between 2003 and 2013 (CDC, 2015.) The
incidence of POW virus was 0.7 cases per year during 1958-1998, and rose to
1.9 cases per year during 1999-2007 (Deardorff et al., 2013.) In affected areas,
the incidence rate ranges from 0.01 per 100,000 to greater than 0.50 per
100,000 (CDC, 2015.) As the incidence rate of POW virus rises, public health
professionals need to be aware of the pathophysiology and biological nature of
the disease, as well as how existing public health regulations are attempting to

stem the spread of disease. The following literature review presents current
scientific knowledge regarding POW virus. Most of the current literature
consists of case studies and histopathological findings, rather than experimental
research, due to the relative rarity of POW virus. However, several studies have
been performed in an effort to estimate the seroprevalence of POW virus in
areas where it has been diagnosed.
Literature Review
Seroprevalence and Distribution
POW virus is a nationally notifiable disease, and all cases are reported to
the Centers for Disease Control by local and state health departments (CDC,
2015.) 57 cases of confirmed POW virus infection were reported between 2004
and 2013; of these cases, 20 were in Minnesota, 17 were in New York, 13 were
in Wisconsin, 2 were from Maine, and there was one case reported in each of
the following states: Massachusetts, New Hampshire, New Jersey, Pennsylvania,
and Virginia (CDC, 2015.) However, there are some other conflicting sources of
information. A case study and literature review by Raval et al (2012) described
4 cases of POW virus infection in a single teaching hospital in North Dakota in
2011. This writer could find no explanation for this discrepancy.

In an effort to quantify the seroprevalence of POW virus (and its variant
DTV) in the New England states, Nofchissey et al (2013) collected blood
samples from white-tailed deer in Connecticut, Maine, and Vermont between
1970 and 2010. White-tailed deer are one of the hosts for I. scapularis, which
spreads the POW virus variant DTV (Nofchissey, et al., 2013.) These blood
samples were tested for neutralizing antibodies via the use of a recombinant
DTV-WNV (West Nile Virus) virus (Nofchissey et al., 2013.) Of the 266 samples
collected in Connecticut, the researchers found that 32% of them contained
neutralizing antibodies that are specific to POW virus/DTV; they also noted that
the antibody prevalence was not constant from year to year, ranging from 0%
in 2000 to 91% in 2009 (Nofchissey et al., 2013.) From the samples collected
from deer in Maine and Vermont, only 13% and 11%, respectively, tested
positive for neutralizing antibodies. The authors suggest that this is due to the
predominance of I. scapularis ticks in Connecticut, leading to greater infestation,
while I. cookei is more predominant in Maine and Vermont (Nofchissey et al.,
2013.) The authors did not speculate as to why there was such variability in
seroprevalence from year to year, though one could guess that the changing
climate may play a role.
Dupuis II et al (2013) performed a similar study in the Hudson Valley area
of New York State. The researchers collected more than 13,500 ticks, along

with blood samples from birds and vertebrates, such as opossums, shrews,
raccoons, and skunks, between the fall of 2007 and the spring of 2012 (Dupuis
II et al., 2013.) The researchers used molecular and virus isolation tests to
identify viral RNA, and the blood samples were tested for POW virus neutralizing
antibodies, using a plaque-reduction neutralization test (Dupuis II et al., 2013.)
While lineage 1 POW virus was not detected in the ticks during this experiment,
lineage 2 DTV was found to be entrenched in the tick population in the 7
counties that comprise the Hudson Valley region (Dupuis II et al., 2013.) This
is largely due to the fact that the number of I. scapularis ticks collected
outnumbered the number of I. cookei ticks by about 100-fold (Dupuis II et al.,
2013.) The DTV infection rate in ticks was as high as 3.84 (expressed as
Maximum Likelihood Estimation/100 ticks) in Putnam County; the researchers
also found that woodchucks, birds, and an opossum displayed serological
evidence of infection (Dupuis II et al., 2013.) The authors suggest that this may
be a conservative estimate due to some protocols used in the experiment that
were less than optimal. This research shows that the lineage 2 variant of POW
virus is firmly established in the tick populations in the Hudson Valley area, and
that further research is required to evaluate how this influences human risk
exposure.
Pathogenesis and Pathophysiology

As noted in the introduction, POW virus is a member of the Flaviviridae
family; like all flaviviruses, it is a single-stranded RNA virus (Ebel, 2010.) It is
transmitted when an infected Ixodes spp. tick bites a human. Studies in mice
have shown that it can take as little as 15 minutes to transmit the virus (Birge
& Sonnesyn, 2012.) Hermance & Thangamani (2015) demonstrated that the
saliva produced by I. scapularis ticks enhances both the transmission and
dissemination of POW virus in mice. POW virus has an incubation period of
approximately 1-4 weeks, with a prodrome that lasts 1-3 days (Birge &
Sonnesyn, 2012.) Prodromal symptoms commonly include headache,
drowsiness, and disorientation (Ebel, 2010.) Other early symptoms include
fever, vomiting, and generalized weakness (CDC, 2015.) For many of those
infected, the virus causes either an asymptomatic infection or a mild illness
resembling the flu (CDC, 2015.) POW virus typically progresses to
meningoencephalitis, which is an infection/inflammation of both the brain and
meninges; its symptoms include altered mental status, seizures, aphasia, paresis,
movement disorders, and cranial nerve palsies (CDC, 2015.) In some cases,
severe neurological impairment can lead to respiratory failure (Ebel, 2010.)
POW virus has a case fatality rate of about 10% and can cause long-term
neurological damage to upwards of 50% of those afflicted (Birge & Sonnesyn,
2012.) Long-term neurological sequelae can include recurrent headaches,

memory problems, hemiplegia, and muscle wasting (Ebel, 2010.) There is no
cure or vaccine for POW virus; the only treatments are supportive therapy and
symptom management (Lani et al., 2014.)
The pathogenesis of POW virus in humans is not entirely understood.
However, we can examine animal studies and research into other flaviviruses
with the hope that we can apply this knowledge to our understanding of POW
virus. Studies in rhesus macaques have demonstrated that POW virus shows
significant neurotropism (it preferentially infects tissues of the nervous system),
particularly for neurons, neuronal processes, and glial cells (Ebal, 2010.) This
results in a significant impairment in neurological function and can induce
seizures and focal neurologic defects (Agamanolis, 2014.) Ebel (2010) notes
that in one case, viral antigen was present in all parts of the neurons, including
the neuronal cell bodies, axons, and dendrites, indicating that viral replication
was occurring in the cells. Yu’s (2014) research on tick-borne encephalitis
showed that after inoculation by an infected tick, the virus begins to replicate
in local tissue. Turtle et al (2012) came to the same conclusion, noting that
flaviviruses tend to replicate in the Langerhans cells of the epidermis. From
there, the virus enters the local lymph nodes, where it begins to replicate in
monocyte-lineage cells, and travels to the brain from there (Turtle et al., 2012.)
It is not yet understood precisely how POW virus and other flaviviruses cross

the blood-brain barrier and enter the central nervous system, but once it enters
the brain, it wreaks havoc.
POW virus causes significant inflammation in the brain and central nervous
system; postmortem histological examination of nervous tissue shows this
inflammation in the frontal, parietal, and occipital cortices, along with the basal
ganglia, pons, and medulla (Ebel, 2010.) The virus also attacks Purkinje cells,
which are the sole avenue of output from the cerebellum (The Neurotransporter
Group, n.d.) This results in some of the movement disorders seen in the
clinical presentation of POW virus disease and can have an effect on the
body’s ability to maintain homeostasis (University of Texas, 1997.) When the
body launches its cell-mediated immune response, CD4+ helper T cells and
CD8+ cytotoxic T cells migrate to the brain, where they tend to do more harm
than good; these lymphocytes infiltrate the brain tissue and concentrate around
the blood vessels (Agamanolis, 2014.) These infiltrates appear to have a
predilection for the gray matter and can cause significant areas of necrosis
(Ebel, 2010.) This necrosis, along with the loss of neurons, explains why so
many POW virus survivors have long-term neurological difficulties (Ebel, 2010.)
Prevention

Since there is no cure or vaccine for POW virus at this time, public health
professionals must focus on preventing tick bites from occurring. In 2013, a
multi-agency initiative was created to combat the spread of tick-borne diseases
like POW virus; it highlights a scientific strategy known as Integrated Pest
Management (IPM). IPM has 5 main elements: 1) risk assessment/biology; 2)
vector surveillance; 3) vector control; 4) monitoring/sustainability; and 5)
adaptive management. (EPA.gov, 2013.) This initiative is intended to promote
collaborative research, increased community outreach, and in the end, a
reduction in the burden of tick-borne disease (EPA.gov, 2013.)
Several preventative interventions are promoted by the Centers for Disease
Control. They recommend using repellents that contain 20-30% DEET (N, N-
diethyl-m-toluamide) on exposed skin and clothing if one is going to be in an
area where ticks are common, such as overgrown areas with tall grass (CDC,
2014.) Usage of 0.5% permethrin products on clothing and camping gear
(tents, etc.) grants longer-lasting protection from tick bites, and is also
recommended (CDC, 2014.) It is also crucial to conduct a visual inspection of
one’s body, to see if any ticks are attached; this should be done for animals
as well as humans (CDC, 2014.) Tick-specific insecticides, known as acaricides,
can be used in residential areas (back yards) to reduce the tick population.

Acaricides products are also available for use on dogs and cats. Regular yard
maintenance is strongly recommended (CDC, 2014.)
Conclusion
Powassan virus can cause significant disease in humans, and is endemic
to more areas than most people realize. There is some evidence that climate
change is resulting in the spread of the ticks that transmit the disease, and it
is not unlikely that medical professionals may see concurrent POW virus and
Lyme disease infections in the near future. There are some major gaps in the
research, especially in the areas of pathogenesis and pathophysiology, due to
the rarity of the virus; much of what we know has been extrapolated from
research into more common and/or well-known viruses. More research into the
use of antiviral medications to treat POW virus is crucial, as is the development
of a vaccine. Until that time, however, public health professionals must be
vocal advocates of personal exposure prevention.

References
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Birge, J. & Sonnesyn, S. (2012.) Powassan virus encephalitis, Minnesota,
USA. Emerging Infectious Diseases, 18 (10). http://www.cdc.gov/eid DOI:
10.3201/eid1810.120621.
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