Prevention of mosquito borne diseases by using mosquito repellents

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Saurabh Dahiya

Saurabh Dahiya

Mosquitoes, the disease transmitters are responsible for around 1.3 million
deaths annually. Diseases such as West Nile Virus, malaria, dengue fever and
yellow fever are transmitted to humans by blood-feeding mosquitoes.

The immediate hypersensitivity and delayed hypersensitivity reactions are
due to mosquito bites. Chemical remedies for mosquito bites are application
of antihistamines, diphenhydramine and topical corticosteroids. An understanding
of vector’s lifecycle and behavioural characteristics guides mosquito control
activities. Meta-N, N diethyl toluamide (DEET) protects against tick bites
and mosquito bites by blocking insect receptors which are used to locate hosts.
DEET products are safest and most effective insect repellents. Naturally occurring
repellants are usually plant volatile oils like pyrethrum. Permethrin
is a synthetic pyrethroid causing nervous system toxicity of the insect leading
to its death. The repellant activities can be measured by the blood-feeding
membrane tests. Safe and effective repellants should be chosen.

1. Introduction about Mosquitoes-The illness carrier

In the English language, the word Mosquito (Span., little fly) dates
back to 1583[1]. The word was adopted to replace the term “biting
flies” to prevent confusion with the “housefly”. It is derived from the word
musca (Latin fly, cf.skt maksh) and is related to the
Italian moschetta and the French mostique[1]. The
mosquito belongs to the family culicidae; these insects have a pair of halteres,
a slender body, and long legs. The females of most mosquito species suck blood
from other animals. Size varies but is rarely greater than 15 mm (0.6 inch).
Mosquitoes weigh only about 2 to 2.5 mg (0.03 to 0.04 grain). A single flight
can last about 4 to 5 minutes. They can fly at about 1.5 to 2.5 km/h (0.9
to1.6 mph) and most species are nocturnal[1]. Mosquitoes are believed
to have evolved around 170 million years ago during the Jurassic era (206-135
million years ago) with the earliest known fossils from the cretaceous era
(144-65 million years ago). The family culicidae belong to the order Diptera
and contains about 3500 species in the 3 subfamilies: Anophelinae (3 genera),
the Culicinae (9 genera and>80% of all the species) and the Toxorhynchitinae
(1 genus). The genera include Nopheles, Culex, Psorophora, Ochlerotatus,
Aedes, Sabethes , Wyeomyia, Culiseta, and Haemagoggus
.Within the sub family
Anophelinae six subgenera are recognized. Stethomyia, Lophopdomyia, Kerteszia,
Nyssorhynchus (all South American), Cellia (Old World only),
and Anopheles (world wide)[1]. Mosquitoes are principally
nectar feeders with only the females requiring a meal of blood, except for
the Toxorhynchites, which never drinks blood [1,2]. This
family includes the largest of the extant mosquito (colloquially referred
to as “mosquito eaters”), the larvae of which are predatory on the larvae
of other mosquitoes. These mosquito eaters have been used in the past as mosquito
control agents with variable success. [1,3]. The female mosquito
(in almost all species) sucks the blood of mammals, including humans. Mosquito
bites often swell up hours after happening, causing a red ringed white bump
about a centimeter in diameter. This bump can itch for days and over-scratching
the bite can cause it to bleed. Continued over-scratching can cause scars.
Mosquito bites can transmit diseases, such as Malaria and West Nile Virus,
so authorities in many areas take measures to reduce mosquito populations
through pesticides or more organic means. An easy way to reduce mosquito populations
in residential areas is the removal of standing water (where mosquitoes breed)
and the use of repellents, such as DEET[1].

Mosquitoes are estimated to transmit disease to more than 700 million
people annually, and will be responsible for the deaths of about 1 in 17 people
currently alive[1,4]. The mosquito genus Anopheles carries the
malaria parasite. Worldwide, malaria is a leading cause of premature mortality,
particularly in children under the age of five, with around 1.3 million deaths
annually. Most species of mosquito can carry the filariasis worm, a parasite
that causes a disfiguring condition (often referred to as elephantiasis) characterized
by a great swelling of several parts of the body; worldwide, around 40 million
people are living with a filariasis disability[1]. Most species
of mosquito can carry the viral disease yellow fever, dengue fever, epidemic
polyarthritis, Rift Valley fever, and West Nile virus. Fortunately, mosquitoes
do not transmit HIV or AIDS. Virus carried by arthropods such as mosquitoes
or ticks are known collectively as arboviruses. West Nile virus was accidentally
introduced into the united states in 1999 and by 2003 had spread to almost
every state[1].

2. Items and activities that attract mosquitoes[5]

• Dark clothing

Many mosquitoes use vision to locate hosts from a distance. Dark clothes
and foliage are initial attractants.

• Carbon Dioxide

We give off more carbon dioxide when we are hot or have been exercising.
A burning candle or other fire is another source of carbon dioxide.

• Lactic Acid

We release more lactic acid when we have been exercising or after eating
certain foods (e.g., salty foods, high-potassium foods).

• Floral or fruity fragrances

In addition to perfumes, hair products, and scented sunscreens, floral fragrance
from     fabric softeners and dryer sheets attract mosquitoes.

• Skin temperature

The exact temperature depends on the type of mosquito. Many mosquitoes are   
attracted to the slightly cooler temperatures of the extremities.

• Moisture

 Mosquitoes are attracted by perspiration because of the chemicals it contain
and also      because it increases the humidity around your body. Even small
amount if water (e.g., moist plants or mud puddles) will draw mosquitoes.
Standing water also allows mosquitoes to reproduce.

3. Mosquito Bite and reasons of irritation

A mosquito’s period of feeding is often undetected; the bite only becomes
apparent because of the immune reaction it provokes. When mosquito bites a
human, she injects saliva and anti-coagulants. For any given individual, with
the initial bite there is no reaction but with subsequent bites the body’s
immune system develops antibodies and the bite becomes inflamed and itchy
within 24 hours. This is the usual reaction in the young children. With more
bites, the sensitivity of the human immune system increases, and an itchy
red hive appears in minutes where the immune response has broken capillary
blood vessels and fluid has collected under the skin. This type of reaction
is common in older children and adults. Some adults can become desensitized
to mosquitoes and have little or no reaction to their bites, while others
can become hyper-sensitive with bites causing blistering, bruising, and large
inflammatory reactions[1].

Visible, irritating bites are due to an immune reaction, i.e., hypersensitivity.
This    hypersensitivity is a reaction of IgG and IgE antibodies to antigens
in the mosquito’s saliva. Some of the sensitizing antigens are common to all
mosquito species, whereas others are specific to certain species. There are
both immediate hypersensitivity reactions (Types I & III) and delayed
hypersensitivity reactions (Type IV) to mosquito bites[1,6].

4. Remedies for mosquito bite

There are several commercially available remedies. A common treatment is
direct application of calamine lotion, which may have a soothing effect, although
its effectiveness is not medically proven. Other insect bite relief sticks
are commercially available. Oral or topically applied antihistamines, and
diphenhydramine in particular, seem to be particularly good at relieving the
itch. Topical corticosteroids such as hydrocortisone and triamcinolone can
help with more severe bites[1].

Another treatment is the direct application of a cloth soaked in very hot
water steaming, but not boiling. The purpose is to trigger the release of
all the histamine in the area at once, thus removing the source of the itching
sensation until more histamine can be reproduced, about 8 to 10 hours[1].

5. Mosquito control programmes of mass scale

An integrated mosquito control program typically includes the following measures,
all guided by surveillance of mosquito populations and knowledge of the mosquito
life cycles[1,7]

· Source reduction- the removal of mosquito breeding habitats

· Habitat modification- manipulating habitats to reduce breeding

· Biocontrol- introducing natural predators of mosquitoes

· Larvicide- using pesticides to reduce larval populations

· Adulticide- using pesticides to reduce adult populations.

Mosquito Life cycle[8]

The first three stages of a mosquito’s four-stage lifecycle take place in
an aquatic environment. A female mosquito lays eggs on the water’s surface,
or on a moist surface in an area that will later be flooded. These eggs hatch
into larvae and progress to the pupa stage, all within the same watery breeding
site. Finally, adult mosquitoes emerge onto the water’s surface and begin
flying. An understanding of the vector’s lifecycle and behavioral characteristics
must guide mosquito control activities in order to maximize natural factors
that reduce mosquito populations and minimize ecological and health impact.
Tackling all points in the vector/infection/re-infection chain is important,
but some measures are more effective, and more acceptable, than others. Reducing
the number of vectors to which people are exposed will be the key. In a hierarchy
of mosquito control options, preference must be given to preventive measures
versus response measures, and to those that are effective and least toxic.

Elimination of mosquito-breeding sites

Mosquitoes breed in stagnant, standing water. The first defense against mosquitoes
in residential environments is to eliminate breeding sites. Potential breeding
sites should be identified around the home. These include bird baths, rain
barrels, eaves troughs, empty planters, pool covers, wanding pools, tires,
blue boxes, pet bowls and children’s toys. Birdbaths, rain barrels, and other
such containers should be emptied twice a week to ensure that mosquito larvae
do not have enough time to develop into adults, and other potential sites
should be removed. Eaves should be regularly cleared of decaying leaves. Businesses
should similarly identify and eliminate potential breeding sites, and municipalities
should do the same in parks and public areas.

Biological Larvae Control

Many fish, birds, bats and insects eat mosquito larvae and adult mosquitoes.
In New York City, larvae-eating “mosquito fish” have been released into wastewater
treatment plants.

Larvicide Options

Larvicides kill mosquito larvae and are considered to be more effective than
adulticides because they target mosquitoes in an isolated environment, before
they are able to transmit viruses between hosts. Bacillus Thuringiensis (Bti)
has been used effectively in many Quebec (Canada). Bti is a naturally occurring
soil bacterium, which contains a toxin that kills when ingested by the mosquito
larvae. Methoprene is another larvicide that acts as a growth regulator, preventing
mosquito larvae form reaching maturity. Its mode of action is considered non-toxic,
it degrades rapidly, and if used according to label instructions should pose
little risk to people. However, methoprene is highly toxic to crustaceans
and insects, moderately toxic to zooplankton, and slightly toxic to fish and
mollusks if use is sustained. Larvicides should only be applied to disturbed
and artificial bodies of water and not to natural and ecologically significant
habitats.

Pesticide spraying

Pesticide spraying aimed at killing adult mosquitoes is at best ineffective
and at worst a public and environmental health hazard. When sprayed from the
air or fogged from vehicles on the ground, pesticides inevitably miss a significant
portion of the target mosquito population. They may, however, contaminate
children’s toys, garden furniture, garden produce, and so on. Moreover it
is not an efficient approach since, even under favorable conditions, mosquito
populations would be reduced by 50-80 percent for no more than a 12-36 hours
period. And, since pesticides kill a variety of non-target organisms, including
natural mosquito predators, they may actually be counter productive and strengthen
vector populations. Malathion is the most commonly used “adulticide”- an aerial
spray aimed at killing adult mosquitoes. It is a broad-spectrum organophosphate
insecticide. Malathion has been associated with birth defects, gastrointestinal
disorders, brain damage, childhood leukemia, and endocrine disruption. Malathion,
a potential groundwater contaminant, is highly toxic to honey bees, amphibians
and insects; and moderately toxic to birds, crustaceans and fish.

6. Mosquito control at personal level with chemically synthesized    mosquito
repellents

DEET remains the gold standard of currently available insect repellents
[9,10]
. The chemical was discovered by US Department of agriculture
scientists and patented by the US Army in 1946.It was registered for use by
the public in 1957.Twenty years of empiric testing of more than 20,000 other
chemical compound has not resulted in another marketed product with the duration
of protection and broad-spectrum effectiveness of DEET [9,10].
DEET is sold under numerous brand names and is available in various forms,
such as cream, lotions, sprays, and extended-release formulations[9,10].
Concentrations of DEET range from about 5% to 100% and, generally, product
with higher concentrations have longer repellent times. [10,11].
However, at some time the correlation between concentration and repellence
is lost. For example, in one study, 50% DEET provided about four hours of
protection against Aedes aegypti mosquitoes, but increasing the concentration
to 100% provided only one additional hour of protection. [10,12].

7. DEET

Meta-N, N-diethyl toluamide, abbreviated DEET (IUPAC name- N, N-diethyl-3-methylbanzamide
with chemical formula-C12H17NO), is an insect-repellent
chemical. It is intended to be applied to the skin or to clothing, and is
primarily used to protect against insect bites. In particular, DEET protects
against tick bites (which transmit Lyme disease) and mosquito bites (which
transmit dengue fever, West Nile fever and malaria)[13].

Mode of action

DEET is believed to work by blocking insect receptors (notably those which
detect carbon dioxide and lactic acid), which are used to locate hosts. DEET
effectively “blinds” the insect’s senses so the biting/feeding instinct is
not triggered by humans or animals which produce these chemicals[13].

The mode of action of many repellents is unclear, but it is believed that
these products do not repel insects, they simply mask or confuse the attractive
signals that humans emit so that mosquitoes are unable to locate us. Mosquitoes
have specific sensory receptors that provide them with the information they
need to detect a source, orient to it to sample a blood meal. Host location
is determined by many factors including lactic acid, ammonia, carbon dioxide,
octenol, phenols, temperature, and humidity[14,15].

8. Safety Record of DEET

DEET has been used for more than 40 years by millions of people worldwide.
Although it has an excellent safety record, there have been sporadic reports
of adverse reaction associated with its use. Most of these have resulted from
accidental exposure, such as swallowing or spraying into the eyes. While most
complaints have involved transient minor skin or eye irritation, rare cases
of toxic encephalopathy have been reported, especially in children, after
ingestion or repeated, prolonged topical application. Adverse reactions are
including headache, nausea, behavioral changes, disorientation, muscle in-coordination,
irritability, confusion, difficulty in sleeping, and even convulsions and
death. However, if DEET products (preferably not the high-concentration products,
such as 75% to 100%)are properly applied and used according to their label
directions, they are considered safe[10].

Studies into the health effects of using DEET in the approved way (as a topical
application) have not shown any significant harm to human health; exposure
to large amounts (by means such as accidental ingestion) has similar effects
to comparable exposure to other pesticides. As DEET is a powerful pesticide,
however, manufacturers of DEET based products advise they not be used under
clothing, on damaged skin, and that the DEET based preparation be washed off
after it is no longer needed or between applications. Current mainstream medical
opinion is that any dangers posed by DEET are greatly outweighed by those
of the serious insect-borne diseases, which DEET helps prevent[13].

9.  Recommendations for using DEET

Despites its hazards, DEET remains one of the safest and most effective insect
repellents available. Here are some tips for using DEET safely[16]

·Reduce your need for repellent. Avoid behaviors that will attract biting
insects (e.g., avoid strenuous exercise or eating lots of high sodium or potassium
foods prior to going outdoors, which increase carbon dioxide release).

·Avoid applying chemicals that attract biting insects (e.g., floral-scanted
perfumes, scented sunscreens, dryer-sheet-scented clothes).

·Where possible, apply DEET-containing repellent to clothes rather than to
skin.    

·Apply DEET in a well-ventilated area.

· Avoid applying DEET to hands, the face, or any injured or sensitive skin.

·Avoid behavior that will lessen the duration of DEET effectiveness (e.g.,
perspiration, rain, mixing with sunscreens).

· When you come indoor, wash off DEET-containing products using warm, soapy
water.

Storage precaution

Remember to store repellents where infants and young children cannot reach
them.

Don’t

·Apply to eyes, lips, or mouth, or over cuts, wounds, or irritated skin.

·Over apply or saturate skin or clothing.

·Apply to skin under clothing.

·Apply more often than directed on the product label[10].     

10. Plant based repellants

These natural products will effectively repel mosquitoes, but they require
more frequent reapplication (at least every 2 hours) and higher concentrations
than DEET[5]. Because of the differences between types of mosquitoes,
products that contain multiple repellents tend to be more effective than those
containing a single ingredient. Natural repellents are usually plant volatile
oils.

• Citronella oil
• Castor oil
• Rosemary oil
• Lemongrass oil
• Cedar oil
• Peppermint oil
• Clove oil
• Geranium oil
• Possibly oil from Verbena, Pennyroyal, Lavender, Pine, Cajeput, Cinnamon,
Basil, Thyme, Allspice, Soybean, and Garlic[5].

Another plant-derived substance, pyrethrum, is an insecticide. Pyrethrum
comes from the flowers of the daisy chrysanthemum cinerariifolium[5].
It is a powerful, rapidly acting insecticide, originally derived from the
crushed and dried flowers of the daisy chrysanthemum cinerariifolium[9,17].

Permethrin

Permethrin is a human-made synthetic pyrethroid[9]. It does repel
insects but works as a contact insecticide, causing nervous system toxicity
that leads to the death or “knockdown”(out of the air) of the insect. The
chemical is effective against mosquitoes, flies, ticks and chiggers. Permethrin
has low toxicity in mammals, is poorly absorbed by the skin, and is rapidly
inactivated by ester hydrolysis[9,18].

Permethrin should be applied directly to clothing or other fabrics (such
as tent walls[9,19] or mosquito nets[9,20]), not to
skin. The spray form is non staining, nearly odorless, and resistant to degradation
by heat or sun and maintains its potency for at least 2 weeks, even through
several launderings[9,21,22]. The combination of permethrin treated
clothing and skin application of a DEET-based repellent creates a formidable
barrier against mosquito bites[9,23,24,25].

11. Measuring the repellent activity

Serious diseases such as West Nile virus, malaria, dengue fever, and yellow
fever are transmitted to humans by blood-feeding mosquitoes, and there is
a need to discover new effective topically applied mosquito repellent compounds
for protection of humans against these disease carriers. To find new repellents,
one might apply test chemicals to the skin of humans in the presence of feeding
mosquitoes. However, this approach is not possible because often the safety
of test chemicals for human use is unknown. This toxicological limitation
severely restricts chemical screening programs for discovery of new and effective
arthropod repellents for human use. To overcome this limitation, (Klun, Jerome,
Kramer and Debboun)[26] designed and developed a blood-feeding
membrane system that mosquitoes feed upon as if it were a human. Tests showed
that when commercial repellents were applied to the blood-feeding membrane,
repellent activities closely resembled results obtained when the commercial
compounds were applied to humans. Thus, the new blood-feeding membrane system
can be used to cheaply and quickly screen large numbers of compounds with
unknown toxicity, and to identify new effective human-use repellent candida
compounds. Promising compounds discovered in this way can be toxilogically
evaluated, and if found safe, they would be ultimately developed for human
use new protectants against disease-carrying mosquitoes.

12. How to choose a mosquito repellent

Look for the list of ‘active constituents’ on the labels of mosquito repellents
to make sure you choose one that is safe and effective. Creams and gels based
on N,-N Diethyl-m-toluamide (DEET) are currently regarded as the best[27].

• Choose repellents with only moderate concentrations of DEET (15 to
20 %).
• Apply the repellent sparingly to exposed skin, especially on children.
• Avoid parts of children’s hand that may touch the eyes or mouth.
• Avoid using the repellent on a daily basis for prolonged periods.
If long-term protection is needed consult your chemist, doctor.
• Stop using the repellent immediately if you suspect an allergic reaction,
and consult your doctor.

13. Things to do to avoid mosquito bites

[10,27]

There are many simple measures to help you avoid mosquito bites. You should
try to:

• Avoid outdoor activity around dusk and dawn when mosquitoes are most
active.
• Wear long loose clothes if mosquitoes are around, preferably in light
colors.
• Use effective mosquito repellents on exposed skin and clothing.
• Use ‘knockdown’ sprays, mosquito coils and plug-in-vaporizing
devices indoors.
• Sleep under mosquito nets treated with repellents or insecticides.
• Use aerosols or pump spray for skin and for treating clothing. These
products provide even application.
• Use liquids, creams, lotions, or sticks to apply more precisely to exposed
skin.
• After outdoor activity, wash DEET-covered skin with soap and water.
• Always keep insect repellents out of the reach of children.
   

14. Things that Lower Repellent Effectiveness

• Many Sunscreens
• Dilution from Rain, Perspiration, or Swimming
• Absorption into the Skin
• Evaporation from Wind or High Temperatures

An ideal insect repellant agent would repel multiple species of biting arthropods,
remain effective for at least 8 hours, cause no irritation to the skin or mucous
membranes, cause no systemic toxicity, be resistant to abrasion and rub-off,
and be greaseless and odorless. No available insect repellent meets all of these
criteria[9].

To be effective, a repellent must show an optimal degree of volatility, making
it possible for an effective repellent vapor concentration to be maintained
at the skin surface without evaporating so quickly that is loses its effectiveness.
Many factors play a role in how effective any repellent is, including the frequency
and uniformity of application, the number and species of the organisms attempting
to bite, the user’s inherent attractiveness to blood-sucking arthropods, and
the overall activity level of the potential host[9,28]. Abrasion
from clothing evaporation and absorption from the skin surface, wash-off from
sweat or rain, higher temperatures, or a windy environment all decrease repellent
effectiveness[9,29,30,31,32,33]. Each 10oC increase in
temperature can lead to as much as a 50% reduction in protection time[9,33].
The repellents currently available must be applied to all exposed areas of skin;
unprotected skin a few centimeters away from a treated area can be attacked
by hungry mosquitoes[9,28,31].

15. Summary

“DEET, (N, N-diethyl-3-methylbenzamide), is most effective and best studied
insect repellent currently on the market. This substance has a remarkable safety
profile after 40 years of world wide use,” but toxic reaction can occur (usually
when the product is misused). When DEET-based repellents are applied in combination
with permethrin-treated clothing, protection against bites of nearly 100% cases
can be achieved. Plant-based repellents are generally less effective than DEET-based
products.

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About Authors:

Saurabh Dahiya

Saurabh Dahiya A-132, Majlis Park, Delhi-110033, India
Mobile phone no- 00 93125 64516, Email- saurabhdahiya@gmail.com

Co Authors :

Prof.Roop K.Khar, Head of Department, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Delhi, India.

Dr. Aruna Chhikkara, Reader, Department of Chemistry , Dayal Singh College, University of Delhi, Lodhi Road, Delhi, India.

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