The Use of Dengue Prevention Techniques to Inhibit an Endemic Presence in the Hawaiian Islands

June 3rd, 2016

Submitted by: Ethan Taylor

etaylor2136@gwmail.gwu.edu

in Partial Fulfillment of the Requirements for the

Master of Public Health Degree,

Milken Institute School of Public Health,

The George Washington University

I. Abstract

Background: Of disease vectors, mosquitoes are the vector known to carry the largest

variety of disease. Among those diseases is the dengue virus. While not endemic to the United

States (U.S), four outbreaks have occurred since 2000 and all have led to transmission to

individuals without a travel history suggesting, at least temporarily, the virus had spread into the

local mosquito population. These events could eventually lead to the disease becoming endemic

in the U.S.

Specific Aims: This critical analysis looks to provide a conglomeration of analytically

evaluated dengue containment techniques that can be used by various public health professionals

and agencies.

Procedures for Reviewing Literature and Conducting Critical Analysis: The information

reviewed for this critical analysis was obtained through the use of various key words, the search

engine Google, and the online Himmelfarb Health Sciences Library at The George Washington

University to delve into containment techniques and answer critical research questions with

sources from the years 2000-2016.

Findings: The 2001-2002 Hawaiian, 2005 Texan, 2009-2011 Floridian, and 2015-2016

Hawaiian dengue outbreaks were explored to examine risk factors, case load, dengue serotype,

and outbreak response techniques in each case. Then, an ecological review was performed to

gain a better understanding of the disease and vector ecology. Following that, containment

techniques, such as habitat management, personal protection, disease surveillance, insecticide

spraying, larvivorous fish, and genetically engineered mosquitos, were all evaluated.

Conclusions: After much review and consideration, the simplest way to contain and

guard against dengue and other neglected tropical diseases spread via vector species Ae. aegypti

and Ae. albopictus is through education of the public and medical personnel. With this

technique, the public will learn their risk, ways to mitigate risk, and understand the importance of

seeking medical attention. Additionally, medical professionals will be more informed on diseases

they might not come in contact with every day, will know how to test for such diseases, and treat

them. As a result of this education, people can reduce mosquito habitat around their homes, wear

clothing to protect themselves, increase disease reporting and surveillance, and thus response.

These events will reduce dengue’s ability to become endemic in the Hawaiian Islands.

II. Background

Vector organisms, typically insects and arachnids, are commonly used as vessels to

promote the spread of 22 different pathogens, which results in more than a billion infectious

disease cases and more than a million deaths worldwide annually (World Health Organization,

2014). Of the organisms known to the World Health Organization (WHO) to carry disease, none

carry more diseases than mosquitos, which can carry one of nine different pathogens depending

on the mosquito species (World Health Organization, 2014). Mosquito-borne pathogens account

for 700 million infectious disease cases annually and a million deaths (Caraballo, 2014) leaving

mosquitos the largest threat to human health of the vector organisms. While malaria receives

much attention and rightfully so, dengue is the fastest growing mosquito-borne illness globally

(Bouri et al., 2012; Centers for Disease Control and Prevention, 2014 [b]). It results in an

estimated 390 million cases a year, which is a 30-fold increase in the past 50 years (Centers for

Disease Control and Prevention, 2014 [b]; World Health Organization, 2015), while primarily

targeting those of low socioeconomic status (Cattand et al., 2006) and children (Centers for

Disease Control and Prevention, 2014 [a]; Gubler, 2002; World Health Organization, 2015).

With 390 million cases annually (Centers for Disease Control and Prevention, 2014 [b]; World

Health Organization, 2015) and 7.3 billion people in the world (United States Census Bureau,

2016), an incidence ratio of 5,342 cases per every 100,000 people globally can be calculated. A

result of this trend, dengue-related disease became the most common febrile illness among

travelers (Schwartz et al., 2008).

Given dengue is a foreign disease to the state of Hawaii, there is not much data on the

effects of dengue in Hawaiian populations. Unlike other diseases common to the United States,

such as diabetes and pneumonia, with many statistics on specific populations of risk, morbidity,

and prevalence, these numbers are unavailable as it pertains to Hawaii specifically. This disease

is threatening an endemic presence in the United States (U.S) and the appropriate preventative

techniques need to be identified to protect the public in the best way possible.

Dengue, spread by Aedes aegypti and Aedes albopictus mosquitoes (Whitehorn et al.,

2015), is a Flavivirus (Martins et al., 2012) that comes in four different serotypes known as

DENV-1, -2, -3, and -4 (Bouri et al., 2012; Effler et al., 2005). These serotypes can lead to

undifferentiated fever, classic dengue fever, dengue hemorrhagic fever and dengue shock

syndrome (Mohammed et al., 2010). Dengue, depending on severity, can result in more mild

symptoms, such as high fever, severe headaches, pain behind the eye, a rash and more, to more

severe symptoms, like vomiting blood, severe abdominal pain, black, tarry stool and additional

ailments (Centers for Disease Control and Prevention, 2012 [a]). According to the Centers for

Disease Control and Prevention (CDC), symptoms occur within four to seven days of being

bitten by an infected mosquito and can last for three to ten days (2014[a]). In order for the

mosquito to become infected, it must bite an infected human because there is no other significant

reservoir host (Petersen, 2015). The bite must occur within a five-day window of high viremia,

which typically begins just prior to symptoms (Centers for Disease Control and Prevention,

2014[a]). From there, the virus has to go through an incubation period of eight to twelve days

before the mosquito can infect humans; the mosquito is infected for the remainder of its life

(Centers for Disease Control and Prevention, 2014[a]).

Due to the habitat range of vector mosquitoes Ae. aegypti and Ae. albopictus, over 2.5

billion people or 40 percent of the global population are at risk of contracting one of the four

dengue serotypes (Liu-Helmersson et al., 2014). These mosquito species are found in tropic and

sub-tropic climates with Ae. aegypti originating in Africa and Ae. albopictus originating in Asia

(Centers for Disease Control and Prevention, 2015). They are able to their spread range through

increased globalization (Gubler, 2002; Struchiner et al., 2015; Wesolowski et al., 2015;

Whitehorn et al., 2015). As it pertains to the U.S, these mosquito vectors are found not only in

the Hawaiian Islands, but the southern U.S, particularly the southeast (Bouri et al., 2012).

Although dengue is not endemic to the U.S, four outbreaks have taken place among three states

over the past 16 years (Adalja, Sell, Bouri, &Franco, 2012; Bouri et al., 2012; Hawaii State

Department of Health, 2016 [a]). Each of these outbreaks included the spread of the disease to

American citizens without a travel history (Adalja, Sell, Bouri, & Franco, 2012; Hawaii State

Department of Health, 2016 [a]) suggesting the virus had, at least temporarily, spread into the

local mosquito population. The risk for these outbreaks continues to rise, as there has been a 15

percent increase in U.S travelers abroad between the time frame of 1998 and 2007 (Mohammed

et al., 2010). Because the disease is not currently endemic in the U.S, there is not a prevalence

ratio.

While the disease eventually spread to citizens without a travel history, it was introduced

each time by a traveler (Adalja, Sell, Bouri & Franco, 2012; Effler et al., 2005; Hawaii State

Department of Health, 2016) and each year 100 dengue cases are imported to the U.S (Bouri et

al., 2012). In all dengue outbreaks in the past 16 years (two in Hawaii, one in southern Florida

and one in Texas), only serotypes DENV-1 and DENV-2 were involved (Bouri et al., 2012;

Hawaii State Department of Health, 2016 [b]). However, in 1999, an outbreak of dengue

occurred in Laredo, Texas involving serotype DENV-3 (Bouri et al., 2012). While there is not an

available vaccine (Mohammed et al., 2010), infection with a specific dengue serotype creates

lifetime immunity to said serotype; however, it provides limited protection against other serotype

infections (Wright & Pritt, 2012).

Although the immune system provides its own protection against dengue after exposure,

it is important to prevent the disease before it causes illness originally. Vaccinations are a major

part of disease prevention. When birth cohorts receive vaccinations at the recommended times,

33,000 deaths and 14 million disease cases are prevented (Department of Health and Human

Services, 2014). With vaccines not currently an available tool to fight dengue, how can dengue

be combatted in the Hawaii? With outbreaks becoming more frequent and approximately 100

cases entering the U.S annually (Bouri et al., 2012), how can Hawaii prevent dengue becoming

endemic in the islands? These questions will become increasingly important as global dengue

prevalence continues to grow.

Due to Hawaii’s tropical climate, close proximity to southeastern Asia, presence of the

vector species, and large number of tourists annually (8.3 million by plane or cruise ships in

2014 [Hawaii Tourism Authority, 2014]), it is necessary for the state to be actively safeguarding

against dengue and prepared to respond to cases and outbreaks in a way that prevents the disease

from spreading into native mosquito populations and eventually into Hawaiians. The results of a

foreign disease becoming endemic could be catastrophic, as there would be a completely naïve

human population for the disease to spread through. Though there are many reports of various

dengue containment techniques, this critical analysis looks to compile these techniques, reports,

and studies to create an in depth investigation of methods to be used as a guide for future dengue

containment in the state of Hawaii.

III. Specific Aims

The aim of the critical analysis is to evaluate the techniques by which exotic mosquito-

borne disease outbreaks, via the vector species Ae. aegypti and Ae. albopictus, are addressed and

contained in order to prevent the spread of the disease to native mosquito populations and then

into citizens without a travel history. While Ae. aegypti and Ae. albopictus can transmit

chikungunya, yellow fever (Center for Disease Control and Prevention, 2012 [b]) and Zika virus

(World Health Organization, 2016 [b]), the disease specifically under evaluation is dengue virus,

which continues to threaten spread as a result of the expansive habitat of the vector mosquito

species, Ae. aegypti and Ae. albopictus. The quick dissemination of dengue virus is leading to

the threat of it becoming endemic, meaning a disease occurring at a foreseeable rate in an area or

people group, in areas where it currently is foreign. The most notable of these areas is the

Hawaiian Islands.

To properly evaluate containment techniques, it is important to understand the ecology of

both the virus and vector. Once viral and vector ecology is understood, one can begin to evaluate

containment techniques, which are quite extensive. Through critical analysis of experimental and

outbreak data, the effectiveness of various containment techniques will be assessed with the goal

of identifying the most effective dengue combatant. These techniques will be important in

attempting to prevent dengue virus from becoming endemic in the Hawaiian Islands and

important in preventing the disease in the public.

IV. Procedures for Reviewing Literature and Conducting Critical Analysis

To gain an understanding of the current dengue containment techniques and disease

distribution, a thorough review was performed regarding previous outbreak responses, the

ecology of the disease, and current prevention techniques within the United States and abroad.

The review evaluated studies of more recent outbreaks and experiments from 2000-2016. This

information was received through government and scholastic reports and studies, in addition to

grey literature.

Research papers and peer-reviewed articles were retrieved using the online library search

service offered through Himmelfarb Health Sciences Library at The George Washington

University. Given the nature of the project, many key words were used in searches. Among those

key words were: dengue, dengue containment, dengue outbreaks in America, Aedes aegypti,

Aedes aegypti control, dengue transmission, larvivorous fish, genetically engineered mosquitos

and more. In order to obtain information from government agencies and grey literature, the

previously mentioned keywords were also used in the search engine Google.

Because of the nature of the disease and the multidisciplinary nature of the public health

field, many journals were utilized. To properly evaluate the options and means for preventing an

endemic dengue presence in Hawaii, entomology, tropical disease, public health, governmental,

vector control, and medical journals were considered and used in compiling the most up-to-date

mosquito and dengue control techniques to protect the public from disease transmission. Having

comprehensively delved into previous actions, current best practices, and the nuances of dengue

transmission, a process will be developed to contain the virus and prevent its autochthonous

transmission.

This critical analysis will be beneficial to various public health entities. Individuals working

in emergency preparedness and response can use it as a reference in their dengue preparation

activities and in their emergency response protocols. Both Hawaiian local and state health

departments can use it to train their staff on dengue containment, better understand the disease,

and begin to work on policies and initiatives to educate Hawaiians. Outbreak investigation teams

can use this critical analysis to learn more about the vector species Ae. aegypti and Ae.

albopictus, dengue, and how to identify potential dengue hotspots and interrupt disease

transmission. Vector control teams can apply the Ae. aegypti and Ae. albopictus ecology and

containment techniques highlighted in this paper to their arsenal of dengue combatants and

mosquito control efforts. The following research questions will be important to address in

moving forward with dengue containment:

What is the current best practices for dengue containment?

Knowing the best practices for dengue containment provides a starting point for the

evaluation of dengue control and has a research backing. Without knowing of current best

practices, there is not a starting point for the critical analysis, there is a lack of knowledge

surrounding dengue control, and an inability to provide a proper critique of current efforts.

Is dengue spread among mosquitos?

Understanding the spread of disease among mosquitos themselves, whether they can spread

disease via vertical transmission, effects the approach to controlling the vector species.

Additionally, it provides more insight into dengue development, spread, ecology, and endemic

threats.

Can dengue go dormant?

If dengue has the ability to go dormant, it will provide additional difficulties in the

diagnostics and treatment of the disease, which could potentially extend the outbreak. Other

mosquito-borne illnesses, such as various species of the malaria parasite, possess this ability

(World Health Organization, 2016 [a]). As a result, multiple treatments are sometimes necessary

to effectively treat malaria in infected individuals.

V. Findings

United States Outbreaks from 2001-2016:

Since 2001, the U.S has experienced four dengue outbreaks. The 2001-2002 outbreak

peaked in September and lasted for eight months, mainly affecting the heavily vegetated and

torrential islands of Maui and Oahu (Adalja et al., 2012; Effler et al., 2005). This outbreak

concluded with 122 confirmed dengue cases involving serotype DENV-1 (Adalja et al., 2012).

Based upon virologic and epidemiologic data, it is thought this outbreak is linked to a dengue

strain from French Polynesia (Effler et al., 2005). It was the first spread of dengue among native

Hawaiians without a travel history since 1944 (Adalja et al., 2012; Bouri et al., 2012). The guilty

vector species being Ae. albopictus (Adalja et al., 2012; Bouri et al., 2012; Effler et al., 2005).

During the outbreak, some key risk factors were discovered. Dengue patients were more likely to

work outside, have traveled to or lived in southeast Asia, the Caribbean, Central and South

America, and live in housing units containing birds (Hayes et al., 2006). The response included

increasing surveillance, educating healthcare providers, health promotion among the public, and

vector control, including larvicides and spraying (Effler et al., 2005).

Advancing to 2005, a dengue outbreak occurred in Brownville, Texas containing 25

confirmed cases (Adalja et al., 2012) and was a part of a larger outbreak, including the Mexican

state of Tamaulipas that totaled 1,251 confirmed cases (Adalja et al., 2012; Bouri et al., 2012).

Of the Brownville cases, 3 were autochthonous (Adalja et al., 2012; Bouri et al., 2012). The

outbreak involved the serotype DENV-2 (Bouri et al., 2012). This outbreak response involved

educational outreach, the testing of blood samples, testing mosquitos, and interviewing (Adalja

et al., 2012). Brownville continued the dengue fight by reducing mosquito breeding grounds and

increasing dengue awareness (Adalja et al., 2012).

Dengue again appeared from 2009 through 2011 in southern Florida. This outbreak

involved the spread of dengue serotypes DENV-1 and -2. (Bouri et al., 2012). These outbreaks

contained the first autochthonous dengue cases in Florida since 1934 (Adalja et al., 2012). The

response was quite extensive. Town hall meetings, door-to-door surveying, press releases, an

information telephone line and television station, and public health programs known as ABCD

(Action to Break the Cycle of Dengue) and “Fight the Bite” posters were all used in containment

and to raise awareness (Adalja et al., 2012).

The most recent outbreak occurred on “the Big Island” of Hawaii and extended from

September of 2015 through February of 2016 (Hawaii State Department of Health, 2016 [a]).

The outbreak resulted in 260 confirmed cases of dengue serotype DENV-1 (Hawaii State

Department of Health, 2016 [b]), 214 of which were in adults and 46 in children (Hawaii State

Department of Health, 2016 [a]). Of these cases, only 25 were visitors to Hawaii (Hawaii State

Department of Health, 2016 [a]). Dr. Lyle Petersen (2016), of the CDC, performed an

assessment of the outbreak. He found surveillance was falling short due to individuals with

dengue-like symptoms not seeking medical care (Petersen, 2016). There were a number of

mosquito breeding sites via man-made structures and natural vegetation (Petersen, 2016). Water

cisterns were present in 80 percent of homes and there was a lacking vector surveillance system

(Petersen, 2016). Hawaii performed many community outreach activities and utilized

exceptional laboratory equipment (Petersen, 2016). Despite 260 cases, Dr. Petersen (2016) was

impressed with the organization of the outbreak response writing, “the coordination of efforts is

one of the best I have witnessed anywhere”.

Vector Ecology:

Vector species Ae. aegypti and Ae. albopictus are well adapted for feeding on human

hosts. Found in urban areas, these mosquitos lay their eggs in half to 400 liter containers, such as

tires, pots, and birdbaths near homes (Han et al., 2015; Mogi, Armbruster, & Fonseca, 2012;

Paiva et al., 2014; Struchiner et al., 2015). Ae. aegypti are daytime biting mosquitos that are

most active at dawn and dusk targeting the ankles and elbows as feeding sites (Centers for

Disease Control and Prevention, 2012 [b]). Aedes mosquitos move very little, in terms of

distance, throughout their life (Bhatt et al., 2013). While the vector does not move vast distances,

infected individuals are still quite mobile allowing for potential spread from infected individual

to mosquito to the next person (Wesolowski et al., 2015). While the vector mosquito enjoys

tropical climates, there are factors that influence the Aedes population. Rainfall and visitor

arrivals were not linked to dengue incidence, but mean and minimum temperature and total

population were (Struchiner et al., 2015). Temperatures above 30 degrees Celsius can reduce the

vectoral abilities of Aedes mosquitos (Struchiner et al., 2015).

Once in the mosquito, the virus begins replication in the midgut and eventually moves

into the salivary glands where it can then be spread into the next person (Cime-Castillo et al.,

2015). While the process is the same in both Ae. aegypti and Ae. albopictus mosquito species,

certain species are more competent in different areas. In terms of viral RNA in the mosquito

midgut, Ae. albopictus had a higher viral RNA concentration of all four dengue serotypes than

Ae. aegypti (Whitehorn et al., 2015). However, this does not mean Ae. albopictus is more

competent at transmitting the disease. Ae. albopictus and Ae. aegypti had an equal likelihood of

developing saliva infected with dengue serotypes DENV-1 and -3. However, Ae. aegypti had a

higher likelihood of having saliva infected with dengue serotypes DENV-2 and -4 (Whitehorn et

al., 2015). This supports the commonly held belief that Ae. aegypti is a more competent dengue

vector than Ae. albopictus (World Health Organization, 2015). While it is important to

understand the competence of the vector species, it is also important to note their ability to

spread dengue to the next generation of mosquitos. This phenomena, known as vertical

transmission, has been documented in Mexico (Martínez et al., 2014), the Philippines (Edillo,

Sarcos, & Sayton, 2015), and Brazil (Martins et al., 2012).

Natural Mosquito Reduction and Habitat Removal:

Source reduction is typically the first line of defense against mosquito vectors (Fonseca et

al., 2013). It involves environmental management and the reduction of mosquito breeding sites

(Esu et al., 2010). Most habitat removal techniques involve removing and preventing standing

water. The CDC (2012 [b]) and WHO (2015) recommend properly disposing of garbage to

reduce standing water, checking weekly for water-filled containers, recycling any containers that

could hold water unnecessarily, and covering objects that could collect water. Routinely

checking gutters for clogs, cleaning bird baths, and filling tree holes can also eliminate mosquito

habitat (CDC, 2012 [b]). By reducing the amount of ideal mosquito habitat, dengue risk is

reduced, as there is less opportunity to encounter the vector species.

While there are many opportunities for residents to remove and tend to potential

mosquito habitat sources around their homes, it is also impossible to eliminate all mosquito

habitat in the Hawaiian biomes. With tropical rainforests located on most of the islands and high

levels of rainfall, staying on top of standing water would be a daily job. Even with covering

potential water containers, such as boats and pots, standing water could still form. Tarp-like

covers, if not tight fitting, can create pockets where water can be held. Some lids have dips in

them that can hold small amounts of water and provide a place for mosquitos to lay their eggs.

Additionally, one cannot control all of the mosquito habitats in the jungle surrounding their

homes.

Personal Protection:

Because Ae. aegypti and Ae. albopictus feed at dawn and dusk and mainly on the wrists

and ankles, there are simple options people can use to protect themselves from mosquito

exposure. The first option is by wearing long-sleeved shirts or long pants to cover their wrists

and ankles. High socks can also be worn to protect the ankles. N,N-Diethyl-meta-Toluamide

(DEET) spray can be applied to clothing items in order to repel mosquitos. Additionally, when

on patios at dawn or dusk, prime Ae. aegypti and Ae. albopictus feeding times, nets can be hung

around gathering areas to prevent mosquito entry. If doors or windows need to be open, screens

should be covering these areas to prevent mosquito access to the home.

The issues here come in the forms of compliance and net management. If screens are left

open, people do not use protective nets or are outside of netting in peak mosquito times, these

barriers will not be effective. Screens and netting needs to be well maintained, as rips, nicks, and

tears can allow mosquito entrance into restricted areas.

Spray:

Insecticides and other sprays are often used and suggested to be used for environmental

treatment and control of vector mosquitos. Additionally, they are recommended by the WHO

(2015) in emergency situations. However, a literature review performed by Esu et al. (2010)

found no evidence for the long-term benefits of spraying. Some studies provided short-term

evidence of vector reduction; conversely, there were also studies that did not show any benefits

(Esu et al., 2010).

Additionally, just as microbes can become antibiotic resistant, so can mosquitos become

resistant to various sprays. This has been seen in malaria control programs (Favia, 2015), is a

particular problem in dengue control with the vector species Ae. aegypti (Marcombe et al.,

2009), and is to a lesser extent with the vector Ae. albopictus (McAllister, Godsey, & Scott,

2012). Marcombe et al. (2014) decided to evaluate the level of Ae. albopictus insecticide spray

resistance in the U.S and did not find evidence of resistance in eight populations within the U.S.

Sprays and water treatments do not just apply to adult mosquitos, but can also be used on

egg and larval stages. This is of great importance, as dormant eggs can help recover a mosquito

population hampered by reduction techniques and can possibly respark outbreaks due to vertical

transmission (Mackay et al., 2015). Sodium hypochlorite (World Health Organization and

United Nations Children’s Fund, 2011) and chlorine (World Health Organization, 2011) are both

safe in low levels of drinking water. This safety allows for its use in water containing mosquito

habitats where each are effective in removing mosquito eggs (Mackay et al., 2015).

While spraying comes with many positives, it is also accompanied by negatives.

Spraying needs done periodically and can contribute to the insecticide resistance currently being

experienced in mosquito populations. This issue would lead to the inability to use sprays any

longer or a need to develop new insecticides. It is also important to keep spray concentrations at

appropriate levels to ensure safety, but effective for mosquito containment purposes. With

frequent rain, animal interactions, and potential children exposure, maintaining a level of safe

concentrations is both important and difficult. With each spray used, it is important to know

potential pathways of human exposure, how persistent the spray is in the body and environment,

and any metabolites that may be produced due to exposure.

Fish:

An approach more holistic than insecticides is the use of larvivorous, larva feeding, fish

to fight Aedes populations. In addition to removing water containing vessels or using insecticides

as a means of vector control, larvivorous fish are a substitute to controlling mosquito breeding in

such containers. Improvements in immature mosquito populations in these containers can be

seen within 24 hours (Han et al., 2015). Depending on container size, guppies, tilapia, and grass

carp are options for using larvivorous fish in the battle to control the dengue vector species (Han

et al., 2015). Use of these types of fish comes with high satisfaction rates. 91 percent of

individuals are pleased with their results (Seng et al., 2008). In order to have a large impact on

vector population and dengue transmission, a large number of containers would need to hold a

species of larvivorous fish (Rodríguez-Pérez, Howard, & Reyes-Villanueva, 2012). Additionally,

if combining the containment techniques of insecticide and larvivorous fish, it is important to

find a combination and concentration that allows the fish to survive with the insecticide present

(Paiva et al., 2014).

Fish, being a natural predator of mosquitos, are a nice option for larger water holding

containers, but again are not without con. Fish are limited to large containers and, should the

water be meant for drinking, would require the water to go through intense filtering and

sterilization to make it safe to drink. The water fish are kept in would need to be changed and the

container cleaned in order to keep water quality at a level suitable to support fish life. Even with

these upkeep chores, there are still other containers unable to handle fish. Tires, tarps, boats, and

other potential water vessels are left untreated, unable to hold fish, and a potential site for

mosquito breeding.

Genetically Engineered Mosquitos:

A more recent development in the fight against dengue and other mosquito-borne

illnesses is the use of genetically engineered, sterile, male mosquitos. Males are released, as

females are the sex that bite humans for a blood meal; releasing females may increase such

nuisance (Bargielowski et al., 2011; Bargielowski, Alphey, & Koella, 2011). It is also important

to note female mosquitos are monogamous and male mosquitos are polygamous, therefore

adding benefit to releasing genetically engineered male mosquitos (Bargielowski, Alphey, &

Koella, 2011). By adding tetracycline to a larval mosquito’s diet, a lethal system is activated

(Thomas et al., 2000). Through Mendelian genetics, releasing males homozygous for the lethal,

dominant trait would guarantee that at least one copy of the lethal gene is passed onto the

offspring (Bargielowski et al., 2011; Bargielowski, Alphey, & Koella, 2011).

Through experimentation, it was found wild-type males can inseminate nearly double the

amount of female mosquitos when compared to their male counterparts (Bargielowski, Alphey,

& Koella, 2011). In a test of fitness, larval mosquitos with the OX513A knockout gene reached

pupations at a level five percent lower than wildtype populations and adults lived four days less

(Bargielowski et al., 2011). Wild-type males also lived longer when caged with refractory

females showing they could potentially identify already inseminated female mosquitos better

than engineered males. Therefore, wild-type males may have used less energy attempting to

court them (Bargielowski, Alphey, & Koella, 2011).

Adult OX513A mosquitos were also smaller than non-engineered mosquitos, but this

could be due to environmental stressors created by crowding in experimental cages

(Bargielowski et al., 2011). However, it is still important as size plays a role in mosquito

reproduction (Bargielowski et al., 2011). Genetically engineered males were able to inseminate

as many females as wild-type males within the first three days, but dropped off from there

suggesting engineered mosquitos regenerate less sperm than wild-type males (Bargielowski,

Alphey, & Koella, 2011). Nevertheless, this will be less of an issue, as males are released at a

10:1 male to female ratio when using this technique (Alphey, et al. 2010). In 2009 and 2010,

Oxitec released engineered, male Ae. aegypti near Grand Cayman and, according to the

company, saw an 80 percent reduction in the Ae. aegypti population (Harris et al., 2011).

While there are potential benefits to genetically engineered mosquito usage, there are also

ethical and ecological implications. Mosquitos are a food source for amphibians, bats, birds, fish,

and other insects (Resnik, 2012). Their absence from the ecosystem could be detrimental to those

species (Resnik, 2012). This absence might not only affect the predatory species of mosquitos,

but other parts of the ecosystem. The ecosystem will have a void that will need to be filled by

another species or organism. Without it, predators may have to leave the area in search of food,

therefore creating more ecological issues.

VI. Conclusions

There are many different and innovative approaches to handling mosquito-borne

diseases, specifically with diseases transmitted by Ae. aegypti and Ae. albopictus, namely

dengue. Each of these techniques comes with many positives and some negatives. They can be

as simple as tidying up around the yard to changing an organism’s genetic makeup in order to

affect its breeding abilities. It is important to consider all of the options available when looking

to prevent, contain, and respond to disease outbreaks. Each situation is different and therefore the

approaches will be different.

Dengue pushes this to another level. Being a tropical and sub-tropical disease, it is

difficult to control due to the habitats provided in jungle and rainforest biomes. With frequent

rainfall comes more areas for mosquitos to replicate and potentially expand a dengue outbreak.

Control and response are always more difficult than prevention. For that reason, it is better to be

proactive than reactive. Each time Hawaii or another state has a case of dengue enter, there is a

chance for autochthonous transmission, and the disease becoming endemic there.

Occam’s Razor suggests the simpler a solution, the more preferential or beneficial it is

(Duignan, 2016). The same is true for prevention techniques. Individuals may mitigate their

dengue risk by taking a personal responsibility for their protection through how they dress and

the items in their yard. Individuals can apply a DEET spray to repel mosquitos and deter biting.

Dressing with long sleeves and long pants can also prevent mosquito bites, as there is less

exposed skin to be fed on. With the ankles and elbows being primary targets for Aedes mosquito

bites (Centers for Disease Control and Prevention, 2012 [b]), it is important to guard those areas.

While there are not many wrist clothing items, high ankle socks or tube socks can be worn to

limit skin exposure in this frequently targeted area. This is even more important as the 2001-

2002 Hawaii dengue outbreak found frequent work outside a major dengue risk factor (Hayes et

al., 2006). While spending time outside, especially during peak Aedes feeding times of dawn and

dusk (Centers for Disease Control and Prevention, 2012 [b]), mosquito nets can be hung around

patios or deck spaces to keep mosquitos away and screen doors and windows can prevent home

access. Additionally, while not all sources of standing water can be eliminated, action can be

taken to store, remove, or cover potential mosquito breeding and egg laying sites. By addressing

those concerns, the mosquito population is limited near the home, as is exposure to mosquitos.

Thus, dengue risk is reduced. These techniques can easily be done by the state of Hawaii in parks

and other outdoor areas to reduce the mosquito population and exposure.

In order to see improvements in the reduction of mosquito habitat in residential areas,

local public health and government agencies need to educate the public on this topic. Florida

implemented many community outreach programs during their 2009-2011 outbreak. While a

great outbreak combatting idea, it is important citizens know how to protect themselves from

dengue prior to an outbreak. From reading Dr. Petersen’s (2016) report on the 2015-2016 dengue

outbreak in Hawaii, Hawaiian citizens would benefit from learning how to manage potential

mosquito habitats around the home.

Dr. Petersen (2016) noted the lack of disease reporting due to people not seeking medical

care. To combat this, it is again important to educate the citizens. Due to the symptoms and

various forms of dengue, individuals with the disease could mistake it for another infection. This

is a major problem. Not treating dengue could lead to the decline of the patient’s health and even

cost them their life. Additionally, by not seeking treatment from a medical care provider, going

about normal life activities, and exposing themselves to mosquitos through being outside, the

patient is at risk of spreading the disease to native mosquito populations that could then spread

the disease via infecting another human or vertical transmission to offspring. By enhancing

surveillance and having more citizens seek medical care, cases can be responded to quicker,

outbreaks can be mitigated, and patterns can be addressed. Disease reporting is critical, as

dengue is listed as an urgent reportable disease by the Hawaii State Department of Health

(Hawaii State Department of Health, n.d). Diseases under this title are to be reported by phone

upon diagnosis and a written report should follow via email or fax within three days (Hawaii

State Department of Health, n.d). Establishing a strong surveillance system is critical to

preventing dengue outbreaks and thus the virus becoming endemic in Hawaii.

Even though the options of personal protection, habitat reduction, education, and

surveillance are the easiest adjustments, there are additional options that can provide benefit.

Larvivorous fish can be put into small ponds and necessary non-drinking water containers to

reduce mosquito larva in such containers. However, this technique requires much work in terms

of maintenance. The efforts to maintain such a set-up far outweighs the benefits, especially when

compared to the benefits and ease of just eliminating the source.

Spraying is a useful tool in emergencies, but should be limited in usage. Its short-term

benefits are good to contain mosquito populations in emergency situations, but the longer term

benefits are greatly lacking. Mosquito populations are beginning to show resistance to pesticides,

so frequent, long-term usage could diminish any current benefits of spraying. Additionally,

spraying must be handled carefully to ensure proper insecticide concentrations to be successful

in mosquito control, yet not harmful to human populations. Therefore, it is important to choose

insecticides carefully, understand their persistence in the environment and people, routes of

exposure, and metabolites produced by the body due to exposure and more.

As for genetically engineered mosquitos, more research needs to be done into the

ecological effects of much an option. Mosquitos play an important role in ecosystems, as a prey

item for a variety of animals. As seen by various invasive species to the Everglades and other

areas, one addition to an ecosystem can throw the whole ecosystem out of whack. The same can

be said about the loss of an organism in an ecosystem. Without the mosquito, due to the release

of sterile, male mosquitos, predator species will have to move out in search of food further

messing up the dynamic of the ecosystem. While only sterile male mosquitos are available for

release in dengue control, other mosquito vectors have been engineered to administer vaccines

and some to prevent the transmission of disease (Resnik, 2012). These types of genetically

engineered mosquitos bring up a variety of ethical issues and the potential for mosquitos to

become vectors for new disease or for diseases to mutate in order to continue use of their vector

species (Resnik, 2012).

The factors surrounding dengue, like all vector borne diseases, are complex. There are

occupational, environmental, epidemiological, biological, and social factors at play. With such a

complex issue, many times individuals go toward complex solutions. However, the prevention of

dengue becoming endemic in the Hawaii Islands has a simple solution mainly through education.

By educating citizens on dengue, its vectors, transmission, and symptoms, they can begin to

understand the risks of dengue and how to protect their homes to limit potential exposure. They

can too understand the necessity of seeing a medical professional once they feel ill. This will

help in surveillance, disease reporting, and will increase case response times. It can lead to the

reduction of mosquito habitat near the home and decreased exposure due to screens and clothing

too. It is also important to ensure medical professionals are well educated about and aware of the

risks of neglected tropical diseases in the Hawaiian Islands. By taking these steps, the Hawaiian

Islands can be safer and more prepared for preventing and containing dengue and other diseases

spread by the vector species Ae. aegytpi and Ae. albopictus.

VII. References

1. Adalja, A. A., Sell, T. K., Bouri, N., & Franco, C. (2012). Lessons learned during dengue outbreaks in the United States, 2001–2011. Emerg. Infect. Dis. Emerging Infectious Diseases, 18(4), 608-614.

2. Alphey, L., Benedict, M., Bellini, R., Clark, G. G., Dame, D. A., Service, M. W., & Dobson, S. L. (2010). Sterile-insect methods for control of mosquito-borne diseases: an analysis. Vector-Borne and Zoonotic Diseases, 10(3), 295-311.

3. Bargielowski, I., Nimmo, D., Alphey, L., & Koella, J. C. (2011). Comparison of life history characteristics of the genetically modified OX513A line and a wild type strain of Aedes aegypti. PLoS One, 6(6), e20699.

4. Bargielowski, I., Alphey, L., & Koella, J. C. (2011). Cost of mating and insemination capacity of a genetically modified mosquito Aedes aegypti OX513A compared to its wild type counterpart. PLoS One, 6(10), e26086.

5. Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O., Myers. M. F., George, D. B., Jaenisch, T., Wint, G. R. W., Simmons, C. P., Scott, T. W., & Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504-507.

6. Bouri, N., Kirk Sell, T., Franco, C., Adalja, A. A., Henderson, D., & Hynes, N. A. (2012). Return of epidemic dengue in the United States: implications for the public health practitioner. Public Health Reports, 127(3), 259-266.

7. Caraballo, Hector (2014). Emergency department management of mosquito-borne illness: malaria, dengue, and west nile virus. Emergency Medicine Practice, 16(5), 1-23.

8. Cattand, P., Desjeux, P., Guzmán, M. G., Jannin, J., Kroeger, A., Médici, A., Musgrove, P., Nathan, M. B., Shaw, A. & Schofield, C. J. (2006). Tropical diseases lacking adequate control measures: dengue, leishmaniasis, and African trypanosomiasis. Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): World Bank. Chapter 23. Available from: http://www . ncbi . nlm . nih . gov/books/NBK11753/

9. Centers for Disease Control and Prevention. (2012 [a]). Symptoms and what to do if you think you have dengue. Retrieved February 14, 2016, from http://www . cdc . gov/Dengue/symptoms/index . html

10. Centers for Disease Control and Prevention. (2012 [b]). Dengue and the Aedes aegypti mosquito. Retrieved February 19, 2016, from http://www . cdc . gov/dengue/resources/30Jan2012/aegyptifactsheet . pdf

11. Centers for Disease Control and Prevention. (2014[a]). Epidemiology. Retrieved February 14, 2016, from http://www . cdc . gov/Dengue/epidemiology/index . html

12. Centers for Disease Control and Prevention. (2014 [b]). World health day—vector-borne diseases. Retrieved February 15, 2016, from http://www . cdc . gov/features/worldhealthday2014/

13. Centers for Disease Control and Prevention. (2015) Entomology and ecology. Retrieved February 15, 2016, from http://www . cdc . gov/dengue/entomologyEcology/index . html

14. Cime-Castillo, J., Delannoy, P., Mendoza-Hernández, G., Monroy-Martínez, V., Harduin-Lepers, A., Lanz-Mendoza, H., Hernández-Hernández, F., Zenteno, E., Cabello-Gutiérrez, C., Ruiz-Ordaz, B. (2015). Sialic acid expression in the mosquito Aedes aegypti and its possible role in dengue virus-vector interactions. BioMed Research International, 2015(1), 1-16.

15. Department of Health and Human Services. (2014). Immunizations and infectious disease. Retrieved February 15, 2016, from https://www . healthypeople . gov/2020/topics-objectives/topic/immunization-and-infectious- diseases

16. Duignan, Brian. (2016). Occam's razor. Encyclopedia Britannica. Retrieved March 8, 2016, from http://www . britannica . com/topic/Occams-razor

17. Edillo, F. E., Sarcos, J. R., & Sayson, S. L. (2015). Natural vertical transmission of dengue viruses in Aedes aegypti in selected sites in Cebu City, Philippines. Journal Of Vector Ecology: Journal Of The Society For Vector Ecology, 40(2), 282-291.

18. Effler, P. V., Pang, L., Kitsutani, P., Vorndam, V., Nakata, M., Ayers, T., Elm, J., Tom, T., Reiter, P., Rigau-Perez, J. G., Hayes, J. M., Mills, K. Napier, M. Clark, G. G., & Gubler, D. J. (2005). Dengue fever, Hawaii, 2001-2002. Emerging Infectious Diseases, 11(5), 742-749.

19. Esu, E., Lenhart, A., Smith, L., & Horstick, O. (2010). Effectiveness of peridomestic space spraying with insecticide on dengue transmission; systematic review. Tropical Medicine & International Health: TM & IH, 15(5), 619-631.

20. Favia, G. (2015). Engineered mosquitoes to fight mosquito borne diseases: not a merely technical issue. Bioengineered, 6(1), 5-7.

21. Fonseca, D. M., Unlu, I., Crepeau, T., Farajollahi, A., Healy, S. P., Bartlett-Healy, K., & Strickman, D., Gaugler, R., Hamilton, G., Kline, D., & Clark, G. G. (2013). Area-wide management of Aedes albopictus. Part 2: gauging the efficacy of traditional integrated pest control measures against urban container mosquitoes. Pest Management Science, 69(12), 1351-1361.

22. Gubler, D. J. (2002). Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends in Microbiology, 10(2), 100-103.

23. Han, W. W., Lazaro, A., Mccall, P. J., George, L., Runge-Ranzinger, S., Toledo, J., Velayudhan, R., Horstick, O. (2015). Efficacy and community effectiveness of larvivorous fish for dengue vector control. Trop Med Int Health Tropical Medicine & International Health, 20(9), 1239-1256.

24. Harris, A. F., Nimmo, D., McKemey, A. R., Kelly, N., Scaife, S., Donnelly, C. A., Beech, C., Petrie, W. D., & Alphey, L. (2011). Field performance of engineered male mosquitoes. Nature biotechnology, 29(11), 1034-1037.

25. Hawaii State Department of Health. (2016 [a]). Dengue outbreak 2015-2016. Retrieved February 15, 2016, from http://health . hawaii . gov/docd/dengue-outbreak-2015/

26. Hawaii State Department of Health. (2016 [b]). Dengue fever frequently asked questions (FAQ) Hawaii Island outbreak. Retrieved February 27, 2016, from http://health . hawaii . gov/docd/files/2015/12/dengue-faq-Hawaii-Island . pdf

27. Hawaii State Department of Health. (n.d). Diseases reportable to the Hawaii department of health. Retrieved March 18, 2016, from http://health . hawaii . gov/docd/files/2013/05/INFECTIOUS-DISEASE-REPORTABLE- FLYER . pdf

28. Hawaii Tourism Authority. (2014). 2014 Annual visitors research report. Retrieved February 16, 2016, from http://files . hawaii . gov/dbedt/visitor/visitor-research/2014-annual-visitor . pdf

29. Hayes, J. M., Rigau-Pérez, J. G., Reiter, P., Effler, P. V., Pang, L., Vorndam, V., & Hinten, S. R., Mark, K. E., Myers, M. F., Street, K., Bergau, L., Meyer, C., Amador, M., Mike, N., Clark, F. G., Biggerstaff, B. J., & Gubler, D. J. (2006). Risk factors for infection during a dengue-1 outbreak in Maui, Hawaii, 2001. Transactions of the Royal Society of Tropical Medicine and Hygiene, 100(6), 559-566.

30. Liu-Helmersson, J., Stenlund, H., Wilder-Smith, A., & Rocklöv, J. (2014). Vectorial capacity of Aedes aegypti: effects of temperature and implications for global dengue epidemic potential. Plos One, 9(3), e89783.

31. Mackay, A. J., Amador, M., Felix, G., Acevedo, V., & Barrera, R. (2015). Evaluation of Household Bleach as an Ovicide for the Control of Aedes aegypti. Journal Of The American Mosquito Control Association, 31(1), 77-84.

32. Marcombe, S., Carron, A., Darriet, F., Etienne, M., Agnew, P., Tolosa, M., Yp-Tcha, M. M., Lagneau, C., Yébakema, A., & Corbel, V. (2009). Reduced efficacy of pyrethroid space sprays for dengue control in an area of Martinique with pyrethroid resistance. The American journal of tropical medicine and hygiene, 80(5), 745-775.

33. Marcombe, S., Farajollahi, A., Healy, S. P., Clark, G. G., & Fonseca, D. M. (2014). Insecticide resistance status of United States populations of Aedes albopictus and mechanisms involved. Plos One, 9(7), e101992.

34. Martínez, N. E., Dzul-Manzanilla, F., Gutiérrez-Castro, C., Ibarra-López, J., Bibiano-Marín, W., López-Damián, L., & Martini-Jaimes, A., Huerta, H., Che-Mendoza, A., Ayora-Talavera, G., & Manrique-Saide, P. (2014). Natural vertical transmission of dengue-1 virus in Aedes aegypti populations in Acapulco, Mexico. Journal Of The American Mosquito Control Association, 30(2), 143-146.

35. Martins, V. P., Alencar, C. H., Kamimura, M. T., de Carvalho Araújo, F. M., De Simone, S. G., Dutra, R. F., & Guedes, M. F. (2012). Occurrence of natural vertical transmission of dengue-2 and dengue-3 viruses in Aedes aegypti and Aedes albopictus in Fortaleza, Ceará, Brazil. Plos One, 7(7), e41386.

36. McAllister, J. C., Godsey, M. S., & Scott, M. L. (2012). Pyrethroid resistance in Aedes aegypti and Aedes albopictus from Port‐au‐Prince, Haiti. Journal of Vector Ecology, 37(2), 325-332.

37. Mogi, M., Armbruster, P., & Fonseca, D. (n.d). Analyses of the Northern Distributional Limit of Aedes albopictus (Diptera: Culicidae) With a simple thermal index. Journal Of Medical Entomology, 49(6), 1233-1243.

38. Mohammed, H. P., Ramos, M. M., Rivera, A., Johansson, M., Muñoz-Jordan, J. L., Sun, W., & Tomashek, K. M. (2010). Travel-associated dengue infections in the United States, 1996 to 2005. Journal Of Travel Medicine, 17(1), 8-14.

39. Paiva, C. N., Lima, J. O., Camelo, S. S., Lima, C. F., & Cavalcanti, L. G. (2014). Survival of larvivorous fish used for biological control of Aedes aegypti (Diptera: Culicidae) combined with different larvicides. Tropical Medicine & International Health: TM & IH, 19(9), 1082-1086.

40. Petersen, L. R. (2015). Interim assessment of the response by the Hawaii state department of health to the dengue outbreak on the island of Hawaii. Retrieved February 14, 2016, from http://health . hawaii . gov/docd/files/2015/12/CDC-Hawaii-assessment_final . pdf

41. Resnik, D. B. (2014). Ethical issues in field trials of genetically modified disease-resistant mosquitoes. Developing World Bioethics, 14(1), 37-46.

42. Rodríguez-Pérez, M. A., Howard, A. F., & Reyes-Villanueva, F. (2012). Biological control of dengue vectors. Integrated Pest Management and Pest Control – Current and Future Tactics, 1(1), 241-270.

43. Schwartz, E., Weld, L.H., Wilder-Smith, A., von Sonnenburg, F., Keystone, J.S., Kain, K.C., et al. (2008). Seasonality, annual trends, and characteristics of dengue among ill returned travelers, 1997-2006. Emerging Infectious Diseases, 14(7), 1081-1088

44. Seng, C. M., Setha, T., Nealon, J., Socheat, D., Chantha, N., & Nathan, M. B. (2008). Community-based use of the larvivorous fish Poecilia reticulata to control the dengue vector Aedes aegypti in domestic water storage containers in rural Cambodia. Journal of Vector Ecology, 33(1), 139-144.

45. Struchiner, C. J., Rocklöv, J., Wilder-Smith, A., & Massad, E. (2015). Increasing dengue incidence in Singapore over the past 40 years: population growth, climate and mobility. Plos One, 10(8), e0136286.

46. Thomas, D. D., Donnelly, C. A., Wood, R. J., & Alphey, L. S. (2000). Insect population control using a dominant, repressible, lethal genetic system. Science, 287(5462), 2474-2476.

47. United States Census Bureau. (2016). Population clock. Retrieved March 19, 2016, from http://www . census . gov/popclock/

48. Wesolowski, A., Qureshi, T., Boni, M. F., Sundsøy, P. R., Johansson, M. A., Rasheed, S. B., Engo-Monsen, K, & Buckee, C. O. (2015). Impact of human mobility on the emergence of dengue epidemics in Pakistan. Proceedings Of The National Academy Of Sciences Of The United States Of America, 112(38), 11887-11892.

49. Whitehorn, J., Kien, D. H., Tran, C. B., Quyen, N. H., Thi, L. V., Le Thi, D., Truong, N. T., Luong, T. T. H., Nguyen, C. V. V., Wills, B., Wolbers, M. & Nguyen, C. V. (2015). Comparative susceptibility of Aedes albopictus and Aedes aegypti to dengue virus infection after feeding on blood of viremic humans: Implications for Public Health. Journal Of Infectious Diseases, 212(8), 1182-1190.

50. World Health Organization. (2011). Guidelines for drinking-water quality. 4th ed WHO, Geneva, Switzerland. 541 p.

51. World Health Organization and United Nations Children’s Fund. (2011). Drinking water: equity, safety and sustainability-joint monitoring program thematic report on drinking water. WHO/UNICEF, Geneva, Switzerland. 62 p.

52. World Health Organization. (2014). Vector-borne diseases. Retrieved January 16, 2016, from http://www . who . int/mediacentre/factsheets/fs387/en/

53. World Health Organization. (2015). Dengue and severe dengue. Retrieved January 19, 2016, from http://www . who . int/mediacentre/factsheets/fs117/en/

54. World Health Organization. (2016 [a]). Malaria. Retrieved February 19, 2016, from http://www . who . int/ith/diseases/malaria/en/

55. World Health Organization. (2016 [b]). Zika virus. Retrieved February 19, 2016, from http://www . who . int/mediacentre/factsheets/zika/en/

56. Wright, W. F., & Pritt, B. S. (2012). Update: The diagnosis and management of dengue virus infection in North America. Diagnostic Microbiology and Infectious Disease, 73(3), 215-220.