Diseases Spread by Insects

or Ticks
Diseases Spread by Insects
or Ticks

Mary E. Miller
Diseases Spread by Insects or Ticks
Copyright © Momentum Press®, LLC, 2018.

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 Abstract
Vector borne diseases transmitted through ticks and mosquitos cause seri-
ous loss of life and significantly impact human populations worldwide.
Each of these diseases is caused by a distinct pathogen, and symptoms vary
depending on the type and severity of infection. The spread of these diseases
occur through the blood meals of tick or mosquitos, where the pathogen
gains access to the human body, usually triggering an immune response that
contributes to disease progression. Understanding the ­interdependence of
pathogen to disease vector along with transmission route to humans shapes
our diagnosis and treatment of these diseases.
This book focuses on five distinct examples of vector borne disease:
Malaria, West Nile, Lyme disease, dengue fever, and bubonic plaque.
Malaria involves the mosquito vector and occurs when mosquito ­transmit
the Plasmodium parasite to humans. West Nile and dengue fever also
involve different mosquito vectors, but in this case transmission of the West
Nile virus or dengue fever virus cause disease. Fleas transmit the bubonic
plague causing bacterium Y. pestis. Lyme disease results from the transmis-
sion of the bacteria Borrelia burgdorferi to humans through the bit of a tick.
In each case we consider current and future issues related to disease progres-
sion, diagnosis, and treatments.

Keywords
B. burgdorferi, Black Plague, Dengue fever, dengue virus, Insect-borne
diseases, Lyme disease, Malaria, Plasmodium, Tick-borne diseases,
West Nile, WNV, and Y. pestis
 Contents
Acknowledgments....................................................................................ix
Introduction...........................................................................................xi
Chapter 1 Symptoms and Diagnosis...................................................1
Chapter 2 Causes and Contributing Factors Complications..............15
Chapter 3 Treatment and Therapy....................................................25
Chapter 4 Future Prospects...............................................................31
Chapter 5 Conclusion......................................................................35
Bibliography..........................................................................................37
Glossary................................................................................................43
About the Author...................................................................................47
Index....................................................................................................49
 Acknowledgments
I would like to thank Malcolm Campbell for the opportunity to make
contributions to this book series. His forward approach to science and
scientific pedagogy is inspiring. I thank my husband David and daughter
Mallory for their patience and support of these efforts. I am fortunate to
work at Rhodes College, which has supported my professional and intel-
lectual development. I take pride that I have worked with outstanding
students, and thank them for inspiring my passion for science education.
My outstanding mentors, colleagues, and collaborators have made it pos-
sible to carry out rigorous research and forward high-impact educational
practices. Specifically, I thank Mitch Smith, Dan Engel, Jeff Becker, Fred
Cross, and Pam Hanson, whose advice and influence have shaped my
professional success. The editorial staff at Momentum Press have been
supportive and kind, and I appreciate their work in the production of this
book. I hope that some aspect of this work is helpful for individuals work-
ing to better understand or manage these devastating diseases.
 Introduction
Transmission of infectious disease requires the introduction and
­reproduction of pathogens, disease-causing microorganisms, in the
human body. Microorganisms are too small to be seen unaided by the
human eye, and include bacteria and viruses. Since transmission is so
critical to the spread of disease in human populations, many diseases
are ­categorized based on how pathogens are spread. Transmission can
occur through many routes; for example, a disease that is spread through
­ingestion of food would be described as a food-borne disease. Many of the
most serious worldwide diseases are transmitted as part of the natural life
cycle of insects and ticks. In these cases, the insects and ticks are consid-
ered ­disease vectors and the illnesses that are transmitted from them to
humans are called vector-borne diseases. The disease itself is caused by
pathogens that are introduced into the human body as the insect or tick
bites the host and takes from the host a blood meal. Since these insects
and ticks require this blood meal to survive, and must get this blood meal
from other organisms, they are described as obligate parasites.
This book describes five examples of vector-borne diseases that
­impair human health: malaria, West Nile, dengue fever, and plague
­transmitted by insects and Lyme disease transmitted by ticks. In each
of these cases, the transmission of a pathogen occurs because these dis-
ease vectors feed on the blood of a human host. The bite of the insect
or tick can cause a l­ocalized reaction, but true harm to the host occurs
after the ­microorganism enters, grows, and replicates inside of the host.
In the United States, each of these infections is a nationally notifiable
disease, meaning that a physician who diagnoses a patient is required to
report the case to the National Notifiable Disease Surveillance Sys-
tem through the Centers for Disease Control and Prevention (CDC).
Obligatory reporting allows for a record of all cases which aids in track-
ing ­infections and recognizing outbreaks of the disease so that control
measures can be taken to reduce the likelihood of disease spread. In this
xii INTRODUCTION

book, the symptoms, diagnoses, and modes of infection transmission

will be d ­ escribed in the context of disease prevention and progression.
Available treatments for the diseases will be presented for each example,
­including methods of controlling disease spread through manipulation of
the ­relevant mosquito, tick, or flea vector.

How Do Insects and Ticks Generally Transmit Disease?

Mosquitos

A mosquito is a winged insect that survives in temperate e­ nvironments

and requires a blood meal to reproduce. The mosquito is able to adapt well
to areas where people live, and in areas where the mosquito p ­ opulation
­carries pathogens, they can be the source of significant ­diseases. The
­ability of mosquitos to spread human diseases is related to their use of
­humans for the life cycle—the ability of the mosquito to grow, develop,
and r­eproduce. The life cycle of the mosquito is fairly complex, and
­requires both water (aquatic stages) and land (terrestrial stages) to grow
and ­reproduce. The female mosquito will lay her eggs in standing water.
Water is a critical aspect to the eggs hatching and the emerging larvae
­remain in the water as they feed on bacteria and organic material until
they develop into pupae, which then develop into adult m ­ osquitos.
­Approximately 8–10 days after the eggs are laid, depending on the
­temperature and availability of food for the larvae, new adult ­mosquitos
are able to lay eggs again, so mosquito populations can increase in short
periods of time. Mosquito eggs are very resilient, able to withstand
months without water. When water is reintroduced, the eggs are able
to hatch soon afterward. Tolerance to dehydration complicates control
measures aimed at reducing mosquito populations since it might be pos-
sible to kill the adult ­mosquitos, but their eggs would remain ­unharmed
by most of these measures. All adult mosquitos survive by getting nutri-
ents from water and the nectar of flowers, but some ­species of female
­mosquitos require the proteins and iron found in blood to make fertile
eggs. For this reason, females of some mosquito species feed on the blood
of birds, reptiles, amphibians, or mammals, including humans. As the
mosquito bites a person, she injects enzymes to prevent the blood from
 INTRODUCTION
xiii

clotting. Scratching bite areas containing these enzymes can cause them
to become red and itchier. However, it is the injection of microorganisms
into the host that has the potential to cause significant disease. People
help the mosquito population thrive because they unknowingly provide
areas of standing water where mosquitos lay eggs and reproduce. There-
fore, it is common to find populations of mosquitos living in close prox-
imity to people, particularly in those areas of the world where the climate
provides good conditions for mosquito reproduction. Many diseases are
spread from mosquitos to humans, such as malaria, dengue fever, West
Nile Virus disease, Zika virus disease, and yellow fever, to name a few. For
this reason, the mosquito presents a serious health concern for humans.

Ticks

In contrast to the mosquito, the tick is not an insect but is an a­ rachnid,

specifically, a spider. Ticks are unable to fly and must wait to attach to
a host after physical contact is made. The tick can detect movement,
­vibrations, body heat, odors, and moisture. The tick will quest or sit on
leaves or grass, positioning itself such that the back legs hold onto foli-
age, while the upper legs are extended outward so the tick can climb
onto a passing host. Once a tick has climbed onto its new host, it will
crawl to find a position on the host to attach, taking between approxi-
mately 10 minutes to 2 hours to prepare to bite and feed. Once the tick
has found a suitable position to bite, it will grasp onto the skin and cut
the surface. The tick will insert a feeding tube with barbs to hold itself
in place and inject a cement-like substance as it feeds. The tick will also
inject an anesthetic-like substance so that the host will not feel the feed-
ing. Depending on the life cycle stage and the type of tick, the feeding can
last for hours to days. During feeding, if the tick carries infectious bacte-
ria, the bacteria can spread to the host. Likewise, if the host is infected,
the bacteria can move into the tick. Once the feeding is complete, the tick
will detach from the host and move through the next stage in its life cycle.
A tick typically lives for 2 to 3 years during which time it will go
through four stages of its life cycle: eggs, six-legged larva, eight-legged
nymph, and adult. After hatching from eggs, the tick will need to have a
new host and feed at each life cycle stage. The earlier six-legged larva stage
xiv INTRODUCTION

usually feeds on small mammals such as mice, but the small (approxi-
mately 2 mm) eight-legged nymph stage often feeds on a human host and
can be a significant source of disease transmission. The adult tick can also
transmit disease but because it is larger, it is usually more quickly removed
from the host, so transmission of disease is less common. Tick nymphs
usually increase in number during the spring and summer months, so the
likelihood of infection also increases during these seasons. Some species
of ticks feed on the same type of hosts for all of their life cycle transitions,
but most feed on a variety of species. In addition to human hosts, many
ticks that are disease vectors can feed on birds, reptiles, or other mammals.

Fleas

Fleas are small, flightless insects. Like ticks and some mosquitos, fleas are
obligate parasites that require a blood meal to survive. Many species of
fleas can feed on humans and some are able to transmit disease during
the feeding. Similar to mosquitos, fleas also have four stages to their life
cycle: eggs, larva, pupa, and adults. Once hatched from eggs, the newly
emerged animals are called larvae and feed on organic material found in
their environment. Larvae will transition through several morphological
stages until they form pupae. Pupae form cocoons, and hatch to release
adult fleas. The larval to adult cycle takes between 3 and 4 weeks to com-
plete. It is the adult flea that must take blood meals from other organisms,
including humans, before it can reproduce. Its first blood meal allows the
female and male fleas to mature, and without feeding on blood, the flea
will die within days. Different species of fleas normally specialize in the
particular host species for feeding, but generally the blood meal can come
from a variety of warm blooded vertebrates, including humans, dogs,
cats, rabbits, squirrels, etc. Fleas are found worldwide, and can spread
disease throughout the world. Since fleas cannot fly, for the adult flea to
gain access to the host, the 0.15 inch animal can jump impressive dis-
tances (up to 8 inches) from one location to another. Fleas jump using
long, jointed hind legs. Unfolding of the jointed hind legs propels the flea
forward. Their propulsion energy comes from a stretched elastic protein
called resilin, which is capable of storing potential energy that can be
released rapidly to extend the legs.
 INTRODUCTION
xv

Why a Blood Meal?

This book focuses on five serious infectious diseases that involve a vec-
tor, either an insect (mosquito or flea) or a tick. In each example, the
vector requires a blood meal to survive or reproduce. When that blood
meal involves a human host, the opportunity exists to transmit infectious
microorganisms from the vector to its human host. In the case of the mos-
quito, only females require a blood meal in order to stimulate the pro-
duction of eggs that will give rise to viable offspring. Several components
of blood are important for mosquito egg production, in particular iron.
Iron found in blood is carried by red blood cells that help move oxygen
throughout the body. In red blood cells, the protein called h ­ emoglobin
binds oxygen because hemoglobin binds tightly to the blood pigment
called heme, or haem. Each heme carries one iron molecule that allows
the heme to attach to molecular oxygen (O2), and therefore allows the
hemoglobin to carry oxygen through the body in red blood cells. Another
source of iron that is taken up by the female mosquito is called ­transferrin.
Transferrin proteins help move iron in and out of the red blood cell. Iron
transporters like transferrin are able to bind to iron at very high affini-
ties and allow iron to be moved from outside cells to inside cells. Female
mosquitos can acquire iron from heme or transferrin and efficiently move
iron to the reproductive organs without experiencing toxicity in other
parts of their body; too much iron is toxic to most animals. Research
continues in order to understand how mosquitos manage to extract iron
in their blood meal and promote egg formation. Other factors obtained
by the mosquito during the blood meal, such as insulin, can persist in the
mosquito and may influence the growth of infectious microorganisms in
the mosquito’s midgut. In the case of the flea, the blood meal allows male
and female fleas to reach sexual maturity. In female fleas, the blood meal
triggers completion of ovary development, whereas in males, an epithelial
plug is released in the testes so that sperm production can proceed. In
addition to these development events, the ability of fleas to mate success-
fully requires a blood meal.
For ticks, the blood meal is required to transition from one devel-
opmental stage to the next once the tick hatches from its egg. With-
out a blood meal, a tick will die, but research continues to more fully
xvi INTRODUCTION

understand the role of specific blood components and their roles in tick
development. Ticks cannot produce their own heme, so like mosquitos
and fleas, the acquisition of heme from the blood meal is required for the
reproduction cycle of ticks. It is likely that the blood meal provides other
essential nutrients or hormones needed for the tick to develop properly.
Scientists have hypothesized that some blood meal components are used
to produce sex pheromones and support female reproductive functions.
The blood meal is also important for male hormone production that con-
tributes to sperm production. For all these reasons, the blood meal is a
critical aspect to the ability of ticks to survive.
 CHAPTER 1

Symptoms and Diagnosis

Malaria
Malaria is a mosquito-borne disease, meaning that it is ­transmitted to
­humans through the Anopheles mosquito bite, as the mosquito feeds.
While there are approximately 430 species of the genus ­Anopheles, only
about 40 are able to transmit malaria to humans. While the f­emale
­Anopheles mosquito feeds, parasites of the genus Plasmodium enter
the human body and reproduce, causing malaria. The World Health
­Organization (WHO) reports that in 2015, over 91 countries ­experienced
populations of individuals where malaria was actively t­ransmitted, and
212 million ­ individuals were diagnosed with malaria, with 429,000
deaths worldwide. The area with the most malaria cases is Africa, where
approximately 90 percent of worldwide malaria cases occur. The CDC
describes malaria in the United States as a curable disease if diagnosed and
properly treated, with about 1,700 cases diagnosed each year. Between
1957 and 2015, only 63 outbreaks of malaria have occurred in the United
States due to a local mosquito to human transmission. However, species
of mosquito capable of carrying Plasmodium exist in the United States,
so concerns remain that malaria could persist again in the United States
(Figure 1.1).
Reproduction of the malaria parasite in humans allows the parasite to
progress through a complicated life cycle that requires both the ­mosquito
and human hosts. The Plasmodium male (microgametocytes) and female
(macrogametophytes) parasites are ingested by the female Anopheles
mosquito during a blood meal from an infected animal. Inside of the
mosquito, the parasites go through a sporogonic cycle. The sporogonic
cycle begins in the mosquito’s stomach, where the male microgametocyte
penetrates the female macrogametophyte resulting in a fertilized zygote.
2 DISEASES SPREAD BY INSECTS OR TICKS

Figure 1.1.  The complex life cycle of the malaria parasite. By Centers
for Disease Control and Prevention (CDC) (http://www.cdc.gov
/malaria/about/biology/) [Public domain], via Wikimedia Commons
https://upload.wikimedia.org/wikipedia/commons/f/f3/Malaria_
lifecycle-CDC.gif

The zygote changes shape becoming elongated and is able to move to

the midgut of the mosquito where it grows and continues to change shape
to form an enclosed sac called the oocyst. The parasites multiply inside
the oocyst sacs until they rupture and release cells called sporozoites.
It is the sporozoites that move to the mosquito’s salivary glands and are
introduced into the human hosts when the mosquito feeds. Once inside
of the human host, the sporozoites migrate to the liver and infect cells
where they develop into schizonts. The schizonts grow and eventually
rupture to release merozoites. Some forms of malaria can lay dormant in
the liver for months or years. While in the liver, the merozoites can infect
erythrocytes (red blood cells) where the parasites multiply as the eryth-
rocytes circulate out of the liver and into the human blood system. While
in human red blood cells, the merozoites develop into yet another stage
of the parasitic life cycle called trophozoite. The trophozoite-infected
red blood cells can also form schizonts, which will eventually rupture
 Symptoms and Diagnosis 3

and release more merozoites. It is during this rupturing stage that the
host develops the characteristic malaria fever symptoms. Alternatively,
the ­trophozoite can develop into a gametocyte (with male and female
­reproductive cells). These gametophytes can be ingested by the mosquito
as she takes a blood meal from the infected individual, continuing the life
cycle of the P ­ lasmodium parasite. If not treated, the infection can p
­ rogress
in a growing population of blood parasites and cause death. When a
­person is infected, uninfected mosquitos can acquire Plasmodium and
­expand the population of malaria vectors.
When a person is infected with the malaria parasite, the first onset
of symptoms can be observed in 7 and 30 days after the bite, depend-
ing in part on the causative species of the Plasmodium infection. The
symptoms of malaria include flu-like symptoms, such as fever, chills,
­fatigue, headaches, sweats, body aches, and nausea. These symptoms can
occur in waves of alternating fever and chills, with the frequency vary-
ing ­depending on the Plasmodium species since these waves of ­symptoms
reflect waves of Plasmodium reproduction in the patient. Additional
symptoms that might occur during a malaria infection include increased
breathing rate, perspiration, enlarged spleen, mild jaundice, and enlarged
liver. Given the similarity of malaria symptoms to other diseases, malaria
symptoms can be misdiagnosed, particularly in countries where malarial
infections are less common. In more serious cases, organ failure can occur
such as acute respiratory distress syndrome or acute kidney failure. Seri-
ous impairment of the blood system can occur where the destruction of
red blood cells results in severe anemia or hyperparasitemia (more than
5 percent infected red blood cells). A patient’s metabolism might also be
severely affected to the point where metabolic acidosis or hypoglycemia
(low blood sugar) occurs. When people suffer from repeated infections,
they may experience an immune response to the Plasmodium, resulting
in hyperactive malarial splenomegaly, which can be characterized by
an enlarged spleen, enlarged liver, anemia, with susceptibility to other
infections. There are some geographical areas where individuals carry the
parasite, but do not experience symptoms. These malaria parasite car-
riers appear to have the ability to fight off the aspects of infection that
give rise to symptoms, but are not able to clear the parasite from their
bodies. These individuals provide an undiagnosed reservoir that amplifies
4 DISEASES SPREAD BY INSECTS OR TICKS

the spread of malaria in unpredictable ways. Malaria carriers might also

present symptoms that are consistent with malaria, carry Plasmodium, but
experience the symptoms due to some other pathogen, which complicates
diagnosis of other diseases.
Confirming that a patient has malaria is essential for treatment and
controlling the spread of disease to the broader population. Diagnosis
begins with the recognition that characteristic symptoms might be due
to malaria because the patient has been in regions where the ­Anopheles
mosquito is known to carry malaria. In countries where malaria is very
common, a person might treat the malaria with no confirmation of
diagnosis. In the United States, where malaria is uncommon, diagno-
sis employs laboratory tests designed to detect the parasite in patient
samples, or detect the patient’s immune response to the presence of the
parasite. ­Visualization of patient blood through a microscope can detect
the p ­ resence of Plasmodium and is considered a reliable diagnostic tool
for malaria. In these cases, the blood is stained so that the parasite can be
more easily observed and trained personnel are able to identify structures
consistent with Plasmodium infection inside red blood cells of the patient.
Collection and handling of patient blood samples can be problematic in
some areas of the world, and research to develop more robust methods of
diagnosis is underway. A negative visual result would lead to new blood
samples being tested every 12 to 24 hours at least three times before con-
cluding an absence of parasite in the patient’s blood. If parasite is found
in the blood sample, then the amount or density of parasite infection is
estimated by determining how many cells contain a parasite after observ-
ing 500 to 2,000 red blood cells. The higher the parasite density, the more
advanced the infection.
In addition to microscopic identification of the parasite, antigen
­detection kits are available to quantify parasite abundance. An anti-
gen is any protein or other molecule that can be bound by an anti-
body. ­Antibodies are produced by human immune cells and can direct
destructive immune cells to destroy antigen that they bind. In this way,
if a parasite is present in the patient, small components of the parasite
­(antigens) will be bound by antibodies and targeted for destruction by the
immune system. In antigen detection kits, commercially available anti-
bodies are used to determine if the Plasmodium antigens are present in the
 Symptoms and Diagnosis 5

patient’s blood. Commercially available antibodies to Plasmodium have

been developed and the U.S. Food and Drug Administration (FDA)–
approved antibody-based tests have been used in hospitals and commer-
cial laboratories since 2007. Antibody-based tests are quick but continue
to be developed to ensure accuracy, and are usually used if microscopic
analysis is not available. An alternative test detects the presence of the
patient’s own antibodies to Plasmodium. In this case, the test does not
indicate the presence of the Plasmodium antigens, but rather indicates
that the patient’s immune system reacted to the Plasmodium antigens at
some point. Since the patient’s immune response will continue to func-
tion even after the infection has been cleared, the serological approach
cannot distinguish between past and current infections of Plasmodium.
In addition to tests that use the patient’s immune response, Plasmodium
can also be detected directly in patient samples by the presence of the
parasite’s genetic material, or DNA. Molecular diagnostic tests that detect
Plasmodium DNA are restricted to high-tech labs and are used to confirm
the specific species of Plasmodium present in the patient after initial diag-
nosis. In the United States, the CDC also recommends that the infecting
Plasmodium be tested for drug resistance. The presence of drug-resistant
strains of Plasmodium in patients presents serious health care concerns for
the individual patient as well as the entire population, since these strains
would be resistant to (not respond to) standard treatments for the disease.

West Nile Virus

West Nile Virus (WNV) disease is a mosquito-borne disease first identi-
fied in northwest Uganda in 1937, but not associated with significant
human disease outbreaks until an epidemic occurred in the Middle East
in the 1950s. In the United States, WNV disease was first observed in
1999, and since that time, cases have been reported in 48 of the 50 states.
WNV primarily spreads along bird migratory routes because birds serve
as a natural virus reservoir. WNV is able to survive in diverse locations,
and is thought to be one of the most widely distributed arboviruses in
the world.
An individual who contracts WNV from a mosquito bite will have a
20 to 30 percent chance of showing symptoms associated with the WNV
6 DISEASES SPREAD BY INSECTS OR TICKS

infection. In an otherwise healthy person, symptoms will occur within

2 to 6 days after the mosquito bite. Immunocompromised individuals
manifest symptoms within 2 to 14 days after exposure. Symptoms can
include fever, headache, body aches, weakness, joint pain, or inflamma-
tion of the brain (called meningitis). Gastrointestinal symptoms and rash
are common too. In approximately 1 percent of infected individuals,
more severe neurological symptoms will develop, such as high fever, neck
stiffness, disorientation, tremors, seizures, or paralysis. Recovery from
these more severe symptoms can take weeks or months. Ten percent of
individuals exhibiting severe symptoms die from their WNV infection.
Infected individuals with cancer, diabetes, hypertension, kidney disease,
or recent organ transplant recipients show increased risk of developing
the more severe WNV symptoms, though the highest risk group is indi-
viduals over 60 years. More severe symptoms caused by WNV are difficult
to distinguish from meningitis caused by other types of virus. In cases of
flaccid paralysis, the symptoms are identical to polio, and are described
as WNV poliomyelitis. WNV-associated Guillain-Barré syndrome
has also been reported such that WNV has invaded the brain or tissues
surrounding the brain. WNV infections that last more than a year have
also been associated with kidney infection by the virus, and the ramifica-
tions of these infections are still under investigation. Research contin-
ues to explore how symptomatic cases of WNV infection impair cells of
the central nervous system. Brain infection likely involves both immune
response–dependent inflammation and direct infection of cells important
for neurological function.
Diagnosis of WNV infection requires detection of associated symp-
toms and exposure to the virus through contact with mosquitos, blood
transfusions, or organ transplants. Tests designed to detect WNV mea-
sure the patient’s immune response to the virus. An immune response
can produce two types of antibody called IgG and IgM. IgM antibodies
specific to WNV can be detected around 3 to 8 days after the initial
WNV infection, and will stay in the patient’s system for 90 days or lon-
ger. IgG antibodies are produced after a second exposure or are produced
after prolong initial infection. A positive result with a WNV antibody
test reflects a past or current infection in the patient. A negative test result
within 8 days of initial infection could be a false negative, so retesting is
 Symptoms and Diagnosis 7

recommended. In some cases, a positive WNV antibody result occurs

because the patient has been infected by a closely related virus such as the
Flavirus St. Louis encephalitis or Japanese encephalitis viruses. It is recom-
mended that a positive WNV antibody result should be confirmed by
other antibody-based tests available at special laboratories, such as the
CDC in the United States. Other tests for WNV include growing virus
in a laboratory from patient samples or detecting viral RNA from patient
samples. Direct detection of the virus in the blood or cerebrospinal fluid
would confirm diagnosis. Confirming tests are important since they can
distinguish between the WNV and closely related viruses and give an
indication of the amount of WNV in patient samples, indicating the
severity of the infection.

Dengue Fever
Dengue fever is caused by the dengue virus, and is a mosquito-borne
disease, meaning that it is transmitted to humans through the bite of
mosquito, primarily Aedes aegypti or to a lesser extent Aedes albopictus.
These two species of mosquitos are different from the vector for malaria.
The disease is restricted to those parts of the world where A. aegypti and
A. ­albopictus normally live, primarily tropical and subtropical regions rang-
ing from latitudes of 35°N and 35°S where the winter temperature is no
colder than 10°C/50°F. The WHO has reported that the annual incidence
of dengue fever has increased since 1996, reaching 1.3 million in 2005,
2.2 million in 2010, and 3.2 million in 2015. Dengue virus is reported as
endemic in over 100 countries. Field collection data suggest that the inci-
dence might be higher than reported, up to 25 percent larger (Figure 1.2).
Dengue virus is thought to have originally infected monkeys and the
virus gained the ability to infect humans approximately 100 to 800 years
ago, but modern-day transmissions between primate and human have
not been observed. The geographical distribution of dengue virus was
restricted prior to 1950, possibly because the disease was spread as mos-
quitos were inadvertently shipped during WWII. After this point, cases
spread throughout Latin America and the Caribbean. Today, the virus is
found in over 100 countries, exposing approximately 40 percent of the
world’s population to potential infection. Dengue fever is estimated by
8 DISEASES SPREAD BY INSECTS OR TICKS

Figure 1.2.  Female Aedes aegypti mosquito vector for dengue fever
in the process of taking a blood meal. By James Gathany [Public
domain], via Wikimedia Commons. https://upload.wikimedia.org
/wikipedia/commons/8/83/Aedes_aegypti_during_blood_meal.jpg

the WHO to be one of the most common diseases spread by mosquito.

While disease progression to the point of death is uncommon in adults,
the vast number of individuals who suffer from dengue fever creates great
economic and social stress.
Most individuals who are infected with dengue virus do not show
any symptoms. When present, symptoms of dengue fever usually occur
between 4 and 7 days after the mosquito bite, and can last up to 10 days.
Infection by dengue virus can result in high fever, rash, bleeding from
the nose or gums, as well as pain in joints, muscle, bone, and behind the
eyes. In more severe cases, dengue hemorrhagic fever can develop where
the fever lasts up to a week and may be followed by additional symptoms
such as difficulty breathing, severe abdominal pain, and vomiting. ­During
dengue hemorrhagic fever, capillaries (small blood vessels) in the body
may break down and leak, putting a strain on the circulatory system. If
not treated, the patient can experience dengue shock syndrome where the
circulatory system fails, which can lead to death. The likelihood of expe-
riencing more serious symptoms associated with dengue virus infection is
increased if a person suffers from diabetes, sickle cell anemia, or asthma.
 Symptoms and Diagnosis 9

In 2009, the WHO released clinical definition guidelines for ­dengue,

creating three primary categories: dengue without warning signs, ­dengue
with warning signs, and severe dengue. For dengue without warning
signs, the patient has a fever with two symptoms that could include
rash, aches and pains, leukopenia (reduced white blood cell count), and
a positive capillary fragility test. The capillary fragility test applies a
tourniquet to the patient and looks for lesions consistent with capillary
breakage. For dengue with warning signs, the patient also experiences one
or more symptoms of pain in the abdomen, vomiting, mucosal vomiting,
enlarged liver, or rapid reduction in white blood cells. A patient catego-
rized as dengue with warning signs would require treatments and close
­monitoring. Patients with progression with severe dengue experience den-
gue shock syndrome, severe bleeding, or severe organ dysfunction. Organ
­dysfunction associated with severe dengue often results in liver or heart
failure. When the central nervous system is affected, loss of consciousness
occurs frequently. Prior to 2009, dengue patients would have been classi-
fied based on guidelines developed in 1997 that were described as dengue
fever, dengue hemorrhagic fever, and dengue shock syndrome.
Diagnosis of dengue fever usually relies on identification of clinical
symptoms and potential exposure to mosquitos that could be carrying
the virus. Frequently, laboratory facilities for more advanced diagnos-
tic ­techniques are not available where dengue-carrying mosquitos are
­endemic. Laboratory tests to confirm diagnosis include detection of the
viral genome, detection of human immune response to the viral infection,
or detection of the virus directly in patient samples by use of antibodies
able to recognize the virus, culturing of the dengue virus, or detection of
viral RNA. The window of opportunity to detect the virus in a patient is
limited to a short period of time where the viral load is high. High viral
load usually occurs just before the onset of symptoms, so a patient is
unlikely to seek clinical help with the infection until after this time period
has passed. Similarly, the detection of viral genome from patient sam-
ples is highly effective, but only early during an infection. The immune
response in patients will be detectable for an extended time period, but
can be confused by false-positive results when patients have been infected
by closely related viruses.
10 DISEASES SPREAD BY INSECTS OR TICKS

Lyme Disease
Lyme disease, also known as borreliosis, is a tick-borne disease, meaning
that it is transmitted to humans by the bite of a tick, specifically the black
legged tick (also called deer tick), Ixodes scapularis and Ixodes ­pacificus.
As the tick feeds, the bacterium Borrelia burgdorferi gains access to
and infects the host. When left untreated, infection can cause severe and
chronic cardiac, neurological, and rheumatologic damage to the patient.
Lyme disease is described by the CDC as the most commonly reported
vector-borne illness in the United States, and ranks it as the sixth most
common disease of any kind reported on the Nationally Notifiable Dis-
ease Surveillance System. In the United States, data from insurance data-
bases suggest that from 2005 to 2010 an estimated 329,000 individuals
were diagnosed with Lyme disease per year. In 2013, a total of 27,203
confirmed cases and 9,104 probable cases were reported.
Symptoms of Lyme disease can vary depending on how far the infec-
tion has advanced. First symptoms occur within 3 to 30 days after the
tick bite and can include fever with rash at the bite location, although
symptoms may occur in the absence of a rash. Additional symptoms can
include chills, headache, fatigue, muscle and joint aches, and swollen
lymph nodes. When a rash occurs, it can take the form of erythema
­migrans (EM) rash. An EM rash initiates at the site of the tick bite,
and will increase in size radiating out from the bite. At times, the rash
will start to clear over time near the bite, producing a characteristic
bulls-eye a­ ppearance, but not everyone with Lyme will get this rash. An
EM rash can increase in size over a period of days and can reach 30 cm,
about a foot, in diameter. A rash associated with the tick bite can occur
anywhere on the body, may feel warm to the touch, but does not usu-
ally hurt or itch. As the infection advances, additional EM rashes can
occur at various locations on the body. Later symptoms of Lyme dis-
ease include severe headaches, neck stiffness, swollen joints, facial palsy
(drooping of one or both sides of the face), irregular heartbeat, dizziness,
shortness of breath, inflammation of brain or spinal cord, nerve pain,
numbness, and impaired short-term memory. In about 1 percent of the
cases, Lyme carditis develops, meaning that the bacteria infect the heart
and impair the electrical signals sustain proper heart contractions. Lyme
 SYmPTOmS AND DIAgNOSIS 11

disease can also impair neurological functions and contribute to Lyme

arthritis. Later stages of Lyme disease can give rise to the wasting away of
skin called acrodermatitis chronica atrophicans. On occasion, patients
who have been diagnosed with Lyme disease and who have undergone
antibiotic treatments will continue to show symptoms of fatigue, joint
pain, or generalized pain for up to 6 months. This condition is called
Posttreatment Lyme Disease Syndrome, and the cause is not under-
stood, though these patients improve over time. Since many of these
symptoms overlap with other conditions such as fibromyalgia or chronic
fatigue syndrome, care should be taken to rule out these alternative causes
before additional antibiotic treatments are used (Figure 1.3).
When an individual shows symptoms associated with Lyme dis-
ease, and has a personal history where they may have been exposed to

Figure 1.3. Erythema migrans in bulls-eye pattern at the site of a tick

bite that subsequently presented as Lyme disease. By Photo Credit:
James Gathany Content Providers(s): CDC/James Gathany [Public
domain], via Wikimedia Commons. https://upload.wikimedia.org
/wikipedia/commons/0/01/Erythema_migrans_-_erythematous_rash_
in_Lyme_disease_-_PHIL_9875.jpg
12 DISEASES SPREAD BY INSECTS OR TICKS

ticks, tests can be carried out to determine if the patient is infected with
B. ­burgdorferi. In the United States, the CDC recommends two blood
tests to detect the causative bacteria, and both tests must produce posi-
tive results to support a Lyme disease diagnosis. The first test, called an
enzyme immunoassay (EIA), determines the presence of an immune
response in the patient to the bacteria. There are several different types of
Lyme EIA tests, but each is able to detect small amounts of patient anti-
bodies in the patient’s blood that bind to the bacteria. Since this first test
is very sensitive, a person with Lyme disease should test positive. How-
ever, this high sensitivity can also mean that a person without Lyme dis-
ease can test positive (a false-positive result), potentially because they have
been exposed to a similar bacterium. For this reason, when test results are
positive or indeterminate, a different test is performed to detect a wider
­selection of immune response proteins that are consistent with infection
by B. ­burgdorferi. This second test can only be useful between the first
4 to 6 weeks of infection, since the immune response being detected takes
that long to develop in the patient. Other tests for Lyme disease exist, and
are commercially available to patients, but the CDC does not describe
them as established and clinically accurate. Examples include urine tests
to detect immune response, culturing or visually inspecting B. b­ urgdorferi
directly through a microscope, and measurements of antibodies in joints.
One complication that can occur with Lyme disease ­patients is ­coinfection
with other pathogens. As a person is infected with B. burgdorferi from a
tick bite, additional microorganisms can be introduced into the person as
well. Possible coinfections with Lyme disease include anaplasmosis, babe-
siosis, and Borrelia miyamotoi infection. The role that coinfection might
have on symptoms or disease progression is an area of current research.

Black Plague
Black plague, or plague, is a flea-borne disease, meaning that the patho-
genic bacteria Yersinia pestis is transmitted to humans through the bite
of a flea. During the 14th century CE, the plague caused more than
50 ­million deaths throughout Europe. Today, approximately 2,000 cases
are reported annually, and concerns of the reemergence of plague are par-
ticularly concerning in certain regions of the world, particularly Africa,
 Symptoms and Diagnosis 13

where infected rodents live in close proximity to humans. A normal flea

bite can cause a delayed reaction in the host skin, usually resulting in
itching within 5 to 30 minutes after the bite. These lesions harden within
a day and usually are not problematic for the patient. More serious symp-
toms arise if the bacterium Y. pestis is transmitted to a person during the
flea bite, and causes an infection resulting in plague.
Human plague disease is described in three major forms depending
on where in the body the initial infection occurs: bubonic plague, septi-
cemic plague, and pneumonic plague. Symptoms of each vary, but are
all caused by infection with the Y. pestis bacteria. The most common is
bubonic plague, which causes symptoms including fever, headache, chills,
weakness, and swelling of lymph nodes. The swollen lymph nodes are
called buboes, hence the name bubonic plague. The lymph node that is
swollen is usually one located close to the original flea bite, where the bac-
teria entered the body. The bacteria multiply inside of the lymph node,
and if not treated, can spread to other parts of the body. In the case of
septicemic plague, patients experience fever, chills, and weakness as well
as abdominal pain, shock, and bleeding into the skin and organs. The
skin can turn black and become necrotic (die), especially in the extremi-
ties like fingers, toes, and nose. Septicemic plague can develop as the pri-
mary form of plague, or develop when bubonic plague is left untreated.
Pneumonic plague symptoms also include fever, headache, and weakness
plus rapidly developing symptoms of shortness of breath, chest pain, and
coughing watery or bloody mucous. Pneumonic plague can develop from
untreated bubonic or septicemic plague, or the bacteria can be transmit-
ted directly from person to person through the inhalation of aerosolized
droplets emitted from an infected person. The bubonic and septicemic
forms of the plague do not spread directly from person to person. In some
cases, pneumonic plague can cause respiratory failure or shock, and there-
fore it is the most lethal form of the disease. When pneumonic plague is
left untreated, the fatality rate can reach 100 percent.
Distinguishing the symptoms of plague from other diseases can be
difficult during the initial stages of the disease. Diagnosis often relies on a
combination of symptoms and travel to or living in plague-endemic areas,
where fleas are more likely to feed on infected mice. Usually, plague mani-
fests as painful buboes near the groin, neck, or armpits 2 to 6 days after
14 DISEASES SPREAD BY INSECTS OR TICKS

infection. Plague-endemic areas include Asia, South America, ­Africa, and

the western part of the United States. In 2017, Madagascar ­experienced
a large outbreak. Diagnosis requires the microscopic identification of
Y. ­pestis isolated from patient blood, sputum, lymph node, or bronchial
samples. Microscopic diagnosis of plague involves staining patient samples
to detect the presence of the bacteria. Stains can include Gram staining,
which allows visualization of the outer cell wall structures of the bacteria.
Y. pestis will be Gram negative (meaning cells retain less of the colored
stain than Gram-positive bacteria). Y. pestis cells stain at the ends of the
bacterial cells, but the center will not, giving a characteristic “safety pin”
appearance. If these microscopic tests are negative, additional serological
tests can be carried out to detect the patient’s immune response to the
presence of the Y. pestis bacteria.
 Index
Acrodermatitis chronica
atrophicans, 11
Aedes aegypti, 7
Aedes albopictus, 7
American dog tick, 20
Amoxicillin, 28
Anopheles, 1
Antibody-dependent enhancement of
infection, 19
Antigen detection kits, 4–5
AQ-13, 32
Arboviruses, 5
Atovaquone, 26
Biofilm, 22
Black plague
causes and complications, 21–23
future prospects, 31–34
symptoms and diagnosis, 12–14
treatment and therapy, 29–30
Borrelia burgdorferi, 10, 19
Borrelia miyamotoi, 12
Borreliosis. See Lyme disease
Brown dog tick, 21
Buboes, 13
Bubonic plague, 13
Capillary fragility test, 9
Capsid, 16
Cefuroxime axetil, 28
Cellular membrane, 16
Chloroquine, 26
Ctenocephalides felis, 22
Culex (Cx.), 17
CYD-TDV targets, 31
DDD107498, 32
Deer tick, 10
DEET, 29
Dengue fever
causes and complications, 18–19
future prospects, 31–34
symptoms and diagnosis, 7–9
treatment and therapy, 28
Dengvaxia, 28
Doxycycline, 28
Enveloped virus, 16
Enzyme immunoassay (EIA), 12
Erythema migrans (EM) rash, 10
Erythrocytes, 2
Flaccid paralysis, 6
Flavirus St. Louis encephalitis or
Japanese encephalitis viruses, 7
Flea bite, transmission by, 22
Fluoroquinolones, 30
Food and Drug Administration
(FDA), 5
Gastrointestinal symptoms, 6
Gene drivers, 33
Gentamicin, 30
Glucose phosphate isomerase, 16
Gram staining, 14
Guidelines for Surveillance,
Prevention, and Control of
West Nile Virus, 28
Hemozoin pigment, 16
Hyperactive malarial splenomegaly, 3
Hyperparasitemia, 3
IgG, 6
IgM, 6
Immune system, exposure of, 19
Jarisch–Herxheimer reaction, 29
KAF-156, 32
Langerhans cells, 18
Lone star tick, 20
Lyme carditis, 10
50 INDEX
Lyme disease
causes and complications, 19–21
future prospects, 31–34
symptoms and diagnosis, 10–12
treatment and therapy, 28–29
Lymph system, 18
Macrogametophytes, 1
Macrophages, 23
Malaria
causes and complications, 15–16
future prospects, 31–34
symptoms and diagnosis, 1–5
treatment and therapy, 25–27
Meningitis, 6
Merozoites, 2
Microgametocytes, 1
Nationally Notifiable Disease
Surveillance System, 10
Nootkatone, 33
Oocyst, 1
Phagocytic cells, 23
Phagocytosis, 23
Plasmodium, 1
appropriate drug, 27
worldwide distribution of, 15t
Pneumonic plague, 13
Posttreatment Lyme Disease
Syndrome, 11
Proguanil, 26
Prophylactic drugs, 26
Pyrethroids, 25
Rocky Mountain wood tick, 20
Schizonts, 2
Septicemic plague, 13
Sporogonic cycle, 1
Sporozoites, 1
Trophozoite, 2
Vector-borne diseases, 31
West Nile virus (WNV)
causes and complications, 16–17
future prospects, 31–34
symptoms and diagnosis, 5–7
treatment and therapy, 27–28
WNV-associated Guillain-Barré
syndrome, 6
WNV poliomyelitis, 6
World Health Organization (WHO), 1
Yersinia pestis, 12
 OTHER TITLES IN OUR HUMAN DISEASES
AND CONDITIONS COLLECTION
A. Malcolm Campbell, Editor
• Genetic Diseases or Conditions: Cystic Fibrosis, The Salty Kiss by Todd T. Eckdahl
• Gradual Loss of Mental Capacity from Alzheimer’s by Mary E. Miller
• Nerve Disease ALS and Gradual Loss of Muscle Function: Amytrophic Lateral Sclerosis
by Mary E. Miller
• Hemophilia: The Royal Disease by Todd T. Eckdahl
• Sickle Cell Disease: The Evil Spirit of Misshapen Hemoglobin by Todd T. Eckdahl
• Auto-Immunity Attacks the Body by Mary E. Miller
• Huntington’s Disease: The Singer Must Dance by Todd T. Eckdahl
• Infectious Human Diseases: Bacteria & Viruses by Mary E. Miller
• Breast Cancer: Medical Treatment, Side Effects, and Complementary Therapies
by KV Ramani, Hemalatha Ramani, Esha Patnaik, SS Alurkar, and Ajaikumar BS
• Acquired Immunodeficiency Syndrome (AIDS) Caused by HIV by Mary E. Miller
• Hereditary Blindness and Deafness: The Race for Sight and Sound by Todd T. Eckdahl
• Down Syndrome: The Amazing Cookie by Todd T. Eckdahl

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