Insect Repellents

Julian Trevino, M.D. Professor and Chair

Department of Dermatology Wright State University Boonshoft School of Medicine

Dayton, OH

DISCLOSURE OF RELEVANT

RELATIONSHIPS WITH INDUSTRY

Julian Trevino, M.D. I do not have any relevant relationships with

industry.

Introduction

Most emerging infectious diseases are arrthropod-borne by mosquitoes and ticks and with few exceptions cannot be prevented by vaccinations (yellow fever vaccine is exception) Ixodes ticks: Lyme disease Aedes aegypti and albopictus (Asian tiger mosquito):

dengue, yellow fever, chikungunya virus, zika virus Culex mosquitoes: West Nile virus

Introduction, cont.

Insect repellent: a chemical or organic agent that makes the atmosphere within 4 cm of human skin so noxious as to discourage contact and biting

Insecticide: a chemical or organic agent that kills insects, typically with a neurotoxin

Some repellents are also insecticides (e.g., permethrin and synthetic pyrethroids)

Introduction, cont.

FDA approves insect repellents EPA approves insecticides

• Many insecticides are approved for outdoor use only • Pyrethroids are the only insecticides approved for indoor

use

Insect repellents

Come in multiple formulations (aerosols, pump sprays, lotions, creams, powders, grease sticks, cloth-impregnated laundry emulsions)

Effective insect repellants: Synthetic chemicals:

• DEET • Picaridin • IR3535 (Skin So Soft)

Plant-derived oils and synthetics • Permethrin • Oil of lemon eucalyptus or PMD • Oil of citronella

DEET

• N, N-diethyl- 3-methylbenzamide

• Most broad-spectrum insect repellant; effective against mosquitoes and ticks • Available in concentrations from 5-100%; 10-35% will provide adequate

protection • Plateau insect repellant effect as DEET concentration exceeds 50% • 50-75% concentrations can result in skin erythema, vesiculobullous skin

necrosis and scarring • Provides vapor barrier that prevents insect from contacting skin

DEET cont.

Will not damage cotton, wool or nylon clothing

Can damage rayon, leather and spandex and dissolve plastic and vinyl upholstery

Crosses placenta; developmental toxicity has not been reported in animals and humans

Pediatric use: use only in children > 2 months age; 10-30% concentration

DEET cont.

Excellent safety record with proper application • 43 case reports on DEET toxicity in

past 5 decades (1956-2008) • 25 with CNS symptoms, one

cardiovascular, 17 cutaneous/allergic reactions (urticarial reactions and hemorrhagic vesiculobullous eruptions associated with application of >50% preparations)

• Deaths (6) associated with intentional ingestion or overuse

DEET cont. In Gulf War used: DEET + permethrin-impregnated clothes + pyridostigmine-bromide (Rx for Nerve Gas) ? = “Gulf War Syndrome”

IR3535 •Ethyl butylacetylaminopropionate- derived from β-alanine •Initially marketed as skin emollient and moisturizer (Avon Skin So Soft) •Protects against mosquitoes, ticks, biting midges, blackflies and sandflies •No reported adverse reactions including no demonstrated developmental toxicities •No specific recommendations for use or avoidance in children or pregnancy

Picaridin (icaridin) •Effective against mosquitoes, ticks, biting flies, chiggers •Provides vapor barrier that deters insect from biting •No serious adverse events reported •Available as 7% solution; 15% aerosol spray •Not recommended in children < 2 years of age

Picaridin cont.

Advantages over DEET: • Lack of chemical odor • Nonsticky or greasy feeling • Lack of damage to clothing or plastics

No reported dermal, solid organ or reproductive toxicity

Botanicals •Oil of lemon eucalyptus- effective against mosquitoes, ticks, biting flies, gnats •Available as 40% pump; efficacy similar to lower concentration DEET (7-15%) •Not for use in children < 3 years old

PMD

PMD (p-menthane-3, 8-diol) is derived from lemon eucalyptus (Corymbia citriodora) extract • only plant-based repellent that has been advocated for use in

disease endemic areas by the CDC due to its proven clinical efficacy to prevent malaria

• has mosquito repellent efficacy and duration equal to that of DEET and may offer better protection against ticks than DEET

• considered to pose no risk to human health • FDA recommends not to use in children under 3 years of age

Permethrin

• Synthetic pyrethroid: derived from chrysanthemums • repellant and insecticide effective against ticks (more effective

than DEET), mosquitoes, flies, biting midges, chiggers, fleas, sandflies

• Mechanism of action requires direct contact with insect • Causes excitation of insect’s nervous system; leads to fatal

paralysis • May be used on clothing, shoes, bed nets, and camping gear

• Requires reapplication after every 5 washings • Long duration mosquito bed nets are available that

maintain effective insecticide levels for 3 years

Permethrin cont.

• Toxicities (including neurotoxicity) at high doses, after massive ingestions or inhalations of permethrin-containing sprays; skin/eye irritation also reported

• No developmental toxicity from permethrin exposure (Pregnancy category B)

• Individuals allergic to chrysanthemums must avoid permethrin use

Citronella

• Obtained from lemongrass • One of the most widely used natural repellents on the market,

used at concentrations of 0.5-20% • Relatively few studies that have been carried out to

determine the efficacy of essential oils from citronella as arthropod repellents.

• Deters nuisance biting from mosquitoes • Ineffective against flies, fleas, biting midges, ticks

Citronella

• Citronella-based repellents only protect from host-seeking mosquitoes for about two hours • Mixing with vanillin reduces the release rate of volatile oil

and prolongs protection time • Nanotechnology and microencapsulation can prolong

protection time • Travelers to disease endemic areas should not be

recommended to use citronella-based repellents

Neem

The EPA has not approved Neem for use as a topical insect repellent.

• Low dermal toxicity, but can cause skin irritation, such as dermatitis when used undiluted

• Is not recommended as an effective repellent for use by travelers to disease endemic areas, although it may confer some protection against nuisance biting mosquitoes.

Natural oils and emulsions

• Bite Blocker, a commercial preparation containing glycerin, lecithin, vanillin, oils of coconut, geranium, and 2% soybean oil can achieve similar repellency to DEET

• Other plant-based oils that have shown some repellent efficacy are coconut oil, palm nut oils and andiroba oil, although all of these three oils are far less effective than DEET

Essential oils

• Essential oils distilled from members of the Lamiaceae (mint family that includes most culinary herbs), Poaceae(aromatic grasses) and Pinaceae (pine and cedar family)are commonly used as insect repellents throughout the globe

• Many oils can cause contact dermatitis • Many commercial repellents contain a number of plant

essential oils either for fragrance or as repellents including peppermint, lemongrass, geraniol, pine oil, pennyroyal, cedar oil, thyme oil and patchouli

Essential oils cont.

• Although essential oils are exempt from registration through the EPA, they can be irritating to the skin and their repellent effect is variable dependent on formulation and concentration.

• Repellents containing only essential oils in the absence of an active ingredient such as DEET should not be recommended as repellents for use in disease endemic areas

• Those containing high levels of essential oils could cause skin irritation, especially in the presence of sunlight

Grapefruit

Component of grapefruit, nootkatone (use in flavoring and fragrances) may be effective against mosquitoes which carry zika virus and Ixodes ticks

Comparative efficacies

• IR3535 superior to DEET for flies and biting midges • PMD and DEET equal in repelling mosquitoes • PMD and picardin superior to DEET in repelling ticks • Permethrin provides better overall protection against tick bites

than DEET and picardin

Comparative efficacies cont.

Most effective use of insect repellants is to layer a topically applied repellant on the skin with permethrin- or other synthetic pyrethroid-impregnated clothing that act on contact as insecticides and provide better and longer-lasting protection against mosquitoes and ticks

Insect repellent and Sunscreen • FDA recommends not to apply

insect repellant under sunscreen and all combination insect repellants and sunscreens should be avoided

• Major concern is that sunscreen needs to be applied more often than the repellant

Repellant use in children and pregnancy

DEET- do not use in children < 2 mos; maximum strength of 30% for all children per AAP

PMD- do not use in children < 3 years Picardin- avoid in children < 2 years

Repellant use in children and pregnancy

DEET: over-application and ingestion can lead to hyperammonemia and encephalopathy; more likely in child with ornithine transcarbamylase deficiency; use of DEET is contraindicated in individuals with urea cycle disorders

IR3535 and permethrin are Pregnancy Category B; other agents not classified

Repellant use in children and pregnancy

Insect Repellents AAP recommendations …the AAP recommends that products for children should contain no

more than 30 percent DEET. • Apply the repellent to clothing or exposed skin only. • Only use spray repellents outside to avoid inhaling them. • Use just enough to cover exposed skin. • Once you return indoors, be sure your child washes with soap and

water to remove the repellent and wash the sprayed clothing before wearing again.

Area and barrier chemical insect repellants

Permethrin-impregnated curtains, screens and bed nets • Effective as adjuncts to topical repellants • Proivde both contact insecticidal and repellant activity

Insecticide vaporizers • Release pyrethroid insecticides • Reduce nuisance biting by mosquitoes • Do not reduce transmission of arthropod-borne diseases

Area and barrier chemical insect repellants

Mosquito coils • Made from compacted pastes or powders containing

pyrethroids or formaldehyde • Smolder for hours, discourage nuisance biting of

mosquitoes • Contaminate atmosphere with particulates and volatile

chemicals • Repeated exposure to smoke may pose significant

risk for lung disease/cancer

Area and barrier chemical insect repellants

Knockdown insecticide sprays • Kill flying insects indoors • No evidence to recommend over other methods

Plant-oil burning candles • May reduce nuisance biting by mosquitoes and flies for

several hours • No evidence to support use over arthropod avoidance,

insect repellants and permethrin-impregnated blinds and curtains

Measures for mgmt, control and prevention of arthropod-borne disease

To minimize outdoor insect bites, CDC recommends: • Wear hats, long-sleeved shirts, long pants (tucked into

boots), boots or covered shoes (not sandals) • Sleep indoors in screened or air-conditioned areas or

under permethrin-impregnated bed nets in inadequate accommodations

• Apply insect repellant throughout the day when outdoors • Remain indoors when arthropods more likely to bite (dawn,

dusk)

Measures for mgmt, control and prevention of arthropod-borne disease

Personal-protective measures to prevent tick-borne diseases include: • Wear light-colored protective clothing to aid in keeping

ticks off skin and making them easier to spot on clothing • Apply picaridin, permethrin-containing repellants, PMD or

IR 3535 to exposed skin • Perform regular whole body tick checks

Measures for mgmt, control and prevention of arthropod-borne disease

• If attached ticks are discovered, remove for expert identification as soon as possible, preferably within 24 hours

• Remove with foreceps or fine-tipped tweezers, gripped close to point of skin attachment with gentle steady traction applied to avoid decapitating ticks and leaving embedded mouthparts with pathogen-filled salivary glands

Community control methods

• Community insecticide “spraying” programs to eliminate mosquitoes are generally not very effective

• Clean up trash- plastic bags, bottle caps, tires; clean gutters to eliminate mosquito breeding sites

• Mosquitoes easy to kill when in water with BTI products (kills mosquitoes/biting flies; will not harm birds, frogs, toads) • BTI = Bacillus thuringiensis subspecies israelensis • Place BTI product in stagnant water (ponds, birdbaths, pots,

whiskey barrel, jugs of water) for mosquito control (Source Howard Garrett- the Dirt Doctor)

Conclusions • With few exceptions, there are no vaccines to prevent mosquito

and tick-borne infectious diseases • Arthropod avoidance, insect repellants and insecticides can

reduce disease transmission to humans • Combine topically applied repellants such as DEET or picaridin

with synthetic pyrethroid-impregnated clothing that act as contact insecticides

• Where exposure to ticks, biting midges, sandflies and blackflies are anticipated, topical repellants containing IR 3535, picaridin or PMD offer better protection than DEET alone

References Diaz JH. Chemical and plant-based insect repellents: efficacy, safety, and toxicity.

Wilderness and Environmental Medicine, 2015. Stanczyk NM, et al. Mosquito repellents for travelers. BMJ 2015;350:h99 doi

10.1136/bmj.h99 Debboun M, Francis SP, Strickman D. Insect repellents handbook second edition. 2015,

CRC PressTaylor and Francis Group, Boca Raton, FL. Rehman JU, Ali A, Khan IA. Plant based products: use and development as repellents

against mosquitoes: a review. Fitoterapia 95 (2014): 65-74. Debboun M, Strickman D. Insect repellents and associated personal protection for a

reduction in human disease. Medical and Veterinary Entomology (2013) 27, 1-9. Katz TM, Miller JH, Hebert AA. Insect repellents: historical perspectives and new

developments. J Am Acad Dermatol 2008;58:865-71. Consumer Reports review of insect repellents 2016: http://www.consumerreports.org/products/insect-repellent/ratings-overview/