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Abstract Ticks are arthropods and the most important vectors of major human diseases after mosquitoes. Due to their impact on public health, in vitro and in vivo assays have been developed to identify molecules with repellent activities on ticks. Repellents are useful to reduce tick bite exposure and the potential transmission of pathogens; they can be used topically or in impregnated clothing. Presently, mainly synthetic molecules are commercialized as skin repellents, e.g., N,N-diethyl-meta-toluamide (DEET), IR3535, picaridin or KBR 3023, and para-menthanediol. Permethrin is largely used for fabric impregnation. Intensive research has been conducted to identify new molecules with repellent activity and more recently, plant-derived molecules, as an alternative to synthetic molecules.
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Tick Repellents for Human Use:
Prevention of Tick Bites
and Tick-Borne Diseases
Fre´de´ ric Pages,
Hans Dautel,
Ge´ rard Duvallet,
Olaf Kahl,
Ludovic de Gentile,
and Nathalie Boulanger
Ticks are arthropods and the most important vectors of major human diseases after mosquitoes. Due to their
impact on public health, in vitro and in vivo assays have been developed to identify molecules with repellent
activities on ticks. Repellents are useful to reduce tick bite exposure and the potential transmission of pathogens;
they can be used topically or in impregnated clothing. Presently, mainly synthetic molecules are commercialized as
skin repellents, e.g., N,N-diethyl-meta-toluamide (DEET), IR3535, picaridin or KBR 3023, and para-menthanediol.
Permethrin is largely used for fabric impregnation. Intensive research has been conducted to identify new mole-
cules with repellent activity and more recently, plant-derived molecules, as an alternative to synthetic molecules.
Key Words: Ticks—Repellents—N,N-diethyl-meta-toluamide (DEET)—IR3535—Picaridin (KBR 3023)—para-
menthanediol—Permethrin—Plant-derived molecules.
Blood-feeding arthropods, insects, and Acari, are im-
dengue, Lyme borreliosis, and rickettsial diseases. Consequently
they are a major cause of morbidity and mortality (Katz et al.
2008, Debboun and Strickman 2013). Because human skin is a
key interface in the transmission of these diseases (Frischknecht
2007), strategies to prevent the contact between human and
vectors have to be considered. Arthropod repellents are an es-
sential part of these strategies. Although mainly developed
against mosquitoes, repellents are more and more considered to
prevent tick-borne diseases (Bissinger and Roe 2010). Following
an overview of the biology of hard and soft ticks and the most
important pathogens transmitted by them, we describe the main
tick bioassays used to identify molecules with anti-tick activities.
We then present the currently available data on synthetic and
plant-derived molecules and their efficacy to repel ticks.
Biology of Ticks
Ticks belong to the subphylum Chelicerata, subclass Acari,
order Acariforms, and suborder Ixodida (Mehlhorn 2001).
Argasidae (soft ticks) and Ixodidae (hard ticks) are two large
families. Their life cycle includes three postembryonic life
stages—larva, nymph, and adult. They are all obligate he-
matophagous ectoparasites, but they differ in their feeding
behavior. Hard ticks take only one blood meal per stage (from
a few days to more than 1 week), whereas soft ticks in their
nymph and adult stages may feed several times for less than
1 h ( Mehlhorn 2001, Schwan and Piesman 2002). The behavior
of ticks is highly variable depending on the species. The most
common strategy is questing behavior. Ticks that hunt re-
spond to stimuli produced by the host, such as carbon di-
oxide, lactic acid, ammonia, heat, shadows, or vibrations
(Sonenshine 1991).
Ticks transmit a large variety of pathogens to humans and
animals. They are considered to be second worldwide after
mosquitoes as vectors of human disease (Piesman and Eisen
2008). Although the risk of acquiring tick bites is high in cer-
tain areas, the risk of pathogen transmission is low if attached
ticks are removed promptly, because for most bacteria, e.g.,
Borrelia and Anaplasma, migration from the midgut to the
salivary glands of the tick must take place before transmission
occurs (Kocan et al. 2008, Piesman and Eisen 2008). However,
Cire OI, St. Denis Cedex 9, Re
´union, France.
Tick-radar GmbH, Berlin, Germany.
´ry—UMR 5175 CEFE, Centre d’Ecologie fonctionnelle et e
´volutive, Montpellier Cedex 5, France.
Laboratoire de Parasitologie-Mycologie, Institut de biologie en sante
´, Centre Hospitalier Universitaire, Angers Cedex 9, France.
EA7290: Virulence bacte
´rienne pre
´coce, Groupe Borre
´liose de Lyme, Membre du Centre National de Re
´rence Borrelia, Universite
Strasbourg, Strasbourg, France.
Volume 14, Number 2, 2014
ªMary Ann Liebert, Inc.
DOI: 10.1089/vbz.2013.1410
tick-borne encephalitis virus is already present in the salivary
glands of unfed vector ticks, so transmission to the host can
occur rapidly (Mansfield et al. 2009). A similar phenomenon
has been described for relapsing fever spirochetes (Schwan
and Piesman 2002), so that in most tick-borne pathogens, a
very low risk of transmission exists earlier than 12 h post-
attachment (Strickman et al. 2009). Because most tick bites
occur at the nymph stage, they can easily go unnoticed.
Repellents can be a good protection for people exposed to
tick bites.
Bioassays to Identify Molecules with Antitick Activities
There are three types of repellent tests: (1) In vitro assays
performed in the absence of any tick host- or host-associated
stimulus; (2) in vitro assays, where some chemical or physical
stimuli attractive for ticks is packaged with the repellent; or (3)
in vivo assays using living hosts (Dautel 2004).
In vitro assays
Laboratory in vitro tests are cheap and can be performed
quickly (Bissinger and Roe 2010) (Table 1). The simplest
versions consist of filter paper placed in a Petri dish, where
one-half of the filter is treated by repellent, while the other
half is untreated. The position of the ticks is recorded at
certain time intervals (Bissinger et al. 2009). Alternatively,
the tick may be placed in the untreated center of the filter
paper surrounded by a circular barrier of repellent; whether
the tick enters or crosses this barrier is recorded (Carroll et al.
2004). Such tests have the disadvantage, however, that it is
unknown whether the ticks under study are in a host-seeking
Host-seeking ticks, particularly those exhibiting ambush
behavior, such as Ixodes ricinus, typically climb a vantage point
when initiating the search for a host. Additionally, I. ricinus,
after transfer to a host, also shows a tendency to walk up on
that host (Dautel et al. 2013). Thus, ticks climbing up in a re-
pellent assay are considered more likely to be in a host-seeking
mode. A climbing assay may consist of a stick (Kaaya et al.
1995, Mwangi et al. 1995, Ndungu et al. 1995), or a vertical filter
paper strip, the upper part of which is treated with repellent
(Carroll et al. 1998, Carroll et al. 2004, Carroll et al. 2011a). A
tick is allowed to climb the stick or filter paper, and whether it
walks a certain distance into the treated zone is recorded.
Some tick attractants can be added in the assays to in-
crease the tick’s motivation to walk onto the repellent-treated
test surface. Jaenson et al. (2005, 2006) and El-Seedi et al.
(2012) used vertical test tubes with their upper opening
covered by a mesh treated with repellent. Ticks were placed
inside the tube, and the observer’s hand was placed above
the mesh. Whether the ticks climb up in response to attrac-
tants from the hand and walk onto the treated mesh is then
recorded. Dietrich et al. (2006) used a similar assay: A short
stick with a cotton tip treated with repellent was placed
vertically inside a vial, with the cotton situated in its upper
third. The upper opening of the vial was covered by a mesh,
and a human hand was placed above to induce the tick inside
the vial to climb up. I. scapularis ticks climbing up to the level
of the cotton tip were scored as not repelled. This assay is
different from the others because the ticks do not have the
opportunity to contact the repellent, but instead respond
solely to the repellent odor in the air.
Table 1. Overview of Some In Vitro Tests Published During the Past Years
Laboratory tests Field tests
Tick behavior Walking Climbing Climbing Climbing Walking/clinging Walking Clinging Clinging/walking
Type of assay Horizontal filter
Vertical filter
vertical stick
Vertical tube Vertical tube with
stick inside
Moving object
Kramer sphere Cloth dragging Volunteers walking
Test surface
Room temperature
35C Room
Host stimuli? No No Human hand
Human hand (short
(from distance)
Movement Human body
(short distance)/
Is the tick
Unknown Probably yes Probably yes Probably yes Yes Most probably
Yes Yes
Carroll et al. 2004,
Bissinger et al.
Ndungu et al.
1995, Carroll
et al. 2011
El Seedi et al.
2012, Jaenson
et al. 2005
Dietrich et al. 2006 Dautel 2004,
Dautel et al. 2013
McMahon 2003 Jaenson et al.
2006, El-Seedi
et al. 2012
Jordan et al. 2012
The temperature of the repellent-treated surface might be higher due to the nearby human body.
A more specialized test system suitable for ticks showing
the ambush type of host seeking is the Moving Object Bioas-
say (MOB) (Dautel et al. 1999). In this assay, the tick clings to a
heated, rotating drum, and whether the tick approaches the
drum, clings to it, and remains on the repellent-treated surface
of the drum or drops off is recorded. Thus, the ticks in this
assay show the typical behavior of ambushing ticks, i.e., tak-
ing advantage of a sudden opportunity to grasp hold. This
assay produces results that are quite close to an in vivo test
with humans (Dautel et al. 2013).
In vivo assays and field tests
In vivo tests with the repellent applied directly onto the host
should yield results that more closely reflect repellent efficacy
under real field conditions. A field test that reflects the real-life
situation best was carried out by Gardulf et al. (2004) in
Sweden. A total of 111 volunteers, all spending at least 2 h per
day outdoors in a tick habitat were involved for a period of 4
weeks. Each volunteer applied 30% Citriodiol
repellent on
their lower legs before starting daily outdoor activities for a
period of 2 weeks (maximum of three applications per day),
and spent another 2 weeks outdoors without any repellent
applied. As a result, 42 tick bites were recorded during the
period, when a repellent was applied, and 112 when it was
not. However, this assay exposes volunteers to a high risk of
acquiring a tick-borne infection and can show substantial in-
dividual variations (e.g., how the product is applied by the
user, or variants in outdoor activity). Moreover, high numbers
of volunteers are required. To reduce these problems, in cer-
tain test protocols, volunteers are advised to perform speci-
fied activities, e.g., walking a certain distance or time at a
specified speed, interrupted by regular tick-check intervals.
Ticks found on a volunteer are not allowed to attach, but are
removed or observed for a certain time period before removal.
While Solberg et al. (1995) used repellent applied onto the
skin, others applied it onto clothes (Schreck et al. 1986, Lane
1989, Evans et al. 1990, Jaenson et al. 2006, Faulde et al. 2008,
Jordan et al. 2012). Unfortunately, systematic studies that
compare the efficacy of a repellent when applied on skin
versus on clothes are missing, making comparison of such
studies difficult.
In vivo studies performed in the laboratory allow control of
temperature, humidity, and light conditions. Usually, patho-
gen-free laboratory ticks of a specified age are used, the
number of ticks contacting the test person is known, and
specific behaviors such as the tick’s walking direction or the
time a given tick spends on treated skin are recorded more
precisely. For evaluation of efficacy, specific test guidelines of
the US Environmental Protection Agency ([EPA] OPPTS
810.3700, available at the EPA website) are available, de-
scribing the minimum data requirements necessary for reg-
istration in the United States. According to this protocol, ticks
are placed on an untreated skin area of a vertically held arm,
and whether the tick walks upward into a treated zone for at
least 3 cm (Carroll 2008) and/or remains there for at least
1 min is recorded. In an assay used by the Stiftung Warentest,
a German consumer care organization, ticks are delivered on
a copper plate and then placed on a vertically held arm or leg
treated with repellent. Whether the tick enters the skin and
walks a distance of at least 5 cm on treated skin within a
certain time period (Schwantes et al. 2008) is recorded. Al-
though both assays seem similar at first sight, they can pro-
duce quite different results (Dautel et al. 2013). A reason
might be that in the EPA protocol ticks have to chose between
staying on untreated skin or walking onto treated skin,
whereas in the Stiftung Warentest assay, the tick’s choice is to
stay either on a copper plate or to walk onto treated skin.
Staying on untreated skin might be a more acceptable alter-
native for a tick than staying on a copper plate, leading to a
higher motivation of the tick to walk onto the treated skin in
the latter case.
More convenient and safer for the volunteers is the fin-
gertip assay, which was developed by Schreck et al. (1995). A
finger is held vertically, touching the ground with its tip. Ticks
enter the untreated tip of the finger, and whether the ticks
walk upward for a certain distance into the repellent-treated
upper zone of the finger is recorded. A number of studies have
used this assay for repellent testing (Pretorius et al. 2003,
Carroll et al. 2005, Carroll et al. 2007, Falo
´tico et al. 2007,
Zhang et al 2009).
Although the described laboratory in vivo studies should
yield reproducible results, it is unknown whether the results
reflect the ‘‘real’’ efficacy of the repellent when used under
field conditions. In an attempt to combine field aspects with a
laboratory test, Carroll et al. (2008) developed a specific assay.
In the laboratory, volunteers stay in a tray with simulated
forest floor containing Amblyomma americanum ticks. Whether
or not the ticks enter the volunteer’s bare foot and walk up-
ward crossing 5 cm of repellent-treated skin is observed. This
test might be suited for ticks of the hunter type.
Last, because tick dragging or flagging is an effective
method to collect exophilic ticks of the ambush type, this
technique might be used for repellent evaluation. To do so, a
certain area of tick habitat is flagged with a repellent-treated
flag and another area of equal size with an untreated flag, and
the number of collected ticks is compared ( Jaenson et al. 2006,
El-Seedi et al. 2012). In this study, the resulting repellency
with I. ricinus ticks was lower than that obtained with the
vertical tube assay ( Jaenson et al. 2006). This might suggest
that a moving object like a drag is a strong stimulus for the
species to cling to, although it might eventually become re-
pelled later on, after some exposure time on the treated flag.
Again, it would be very interesting to compare the repellent
efficacy evaluated by this method with that of an in vivo test.
Repellents for Human Use, Available on the Market
A repellent is a natural or synthetic substance that causes an
arthropod to go away from its initial target. Therefore, it limits
or even prevents the human–vector contact. Repellents can be
classified into two categories—plant extracts or essential oils
and synthetic products.
The effective dose, most often expressed as the ED
, describes the inherent repellency of a substance, irre-
spective of how long repellency lasts. The complete protection
time is defined as the time from application of a given repel-
lent until (1) the first tick is not repelled, or until (2) the first
tick ‘‘confirmed’’ by a second tick within a certain time in-
terval is not repelled. Ideal characteristics of a repellent are
prolonged efficacy against arthropods, lack of toxicity, ab-
sence of damage to clothing and plastics, and proven resis-
tance to washing. The US Centers for Disease Control and
Prevention, and the European community (Directive 98/8)
recommend the same molecules as topical repellents: N,N-
diethyl-meta-toluamide (DEET), picaridin (KBR 3023),
p-menthane-3,8-diol (PMD), and IR3535 (Table 2). Indalone,
dimethyl phthalate (DMP), and ethyl hexanediol (EHD) have
been removed from the market either due to their toxicity or to
their inefficacy (Bissinger and Roe 2010, PPAV 2011).
Characteristics of synthetic molecules
DEET is the oldest repellent currently used. Marketed in
1957 in the United States, DEET is a colorless, slightly oily
solvent. It can alter plastics and synthetic fabrics. DEET is
absorbed in the superficial layers of the skin, and around 5%
of the product has systemic diffusion that can be increased
with the simultaneous use of sunscreen (Katz et al. 2008).
Microencapsulation reduces the potential toxicity of DEET
in humans (Kasting et al. 2008) and a long-lasting formula,
(3M), has been developed for the military (Katz
et al. 2008). The addition of cyclodextrins reduces evaporation
and increases the duration of action without increasing skin
penetration (Proniuk et al. 2002). Concentrations of 10–35%
provide an adequate protection, with a plateau at 50%. DEET is
regularly used by 30% of the people in the American market,
has been commercialized for over seven decades, and its safety
record is reliable (Katz et al., 2008). The concentration has to be
adjusted according to the age of the user (PPAV 2011).
PMD (also known as paramenthanediol) is derived from
lemon eucalyptus (Eucalyptus maculata citriodora or Cor-
ymbia citriodora). PMD is known as Quwenling in China and
in the United States as Oil of Lemon Eucalyptus through its
EPA registration. PMD is now synthesized. The full che-
mical name, 2-(2-hydroxy-2-methyl)-5-methyl-cyclohexanol
(PMDRBO) is a cis and trans mixture of p-menthane-3,8-diol.
In reports of Canadian, American, or European agencies, no
sensitization or irritation is observed, but this compound can
be irritating to the eyes. Registered in the United Kingdom by
Citrefine as Citriodiol
, it contains 64% of PMD. This product
is not as effective against ticks as DEET or picaridin.
Table 2. Most Important Natural and Synthetic Repellents Already Marketed or in Development
Molecules Development Concentration Disadvantages Advantages Other specificity
Synthetic repellents registered in US, Canadian, and European agencies
DEET 1953 10–50% Oily, alters
irritating for
the eyes
cheap, broad-
DEET 33% =slow
release polymer =
Picaridin or KBR3023
from piperidine)
1980s (Bayer) 20–30% Not so efficient
on ticks
Broad spectrum,
does not alter
plastics, low
IR3535 or EBAAP 1975 (Merck) 20–35% Low repellency
at low
Safe, good
Would be the
best on ticks;
related to
Most important
marketed plant-derived
(Quwenling) Citriodiol
20–30% Contains citral
(skin irritating),
eye irritating
Permethrin (pyrethrinoids) 1979 0.5% More toxic than
repellent, should
not be applied
to skin
Clothing repellent,
Most-studied tick repellent compound derived from plants
Carvacrol NA Grapefruit oil
and Alaskan
1-alpha-terpineol NA Cleome monophylla
Tanacetum vulgare
2007 7.75% Lycopersicon hirsutum,
wild tomato
Nootkatone 0.0458 (wt/vol) Chamaecyparis
yellow cedar
Dodecanoic acid (DDA),
10% Coconut and palm
kernel oil
Sources: Katz et al. 2008, Strickman et al. 2009, Bissinger and Roe 2010, Debboun and Strickman 2013.
NA, not available.
IR 3535, marketed by Merck in 1973, is also known as EBAAP
or by its chemical name 3-(N-acetyl-N-butyl)aminopropionic
acid ethyl ester. According to the criteria of the EU Directive
67/548/EC on chemicals, IR3535
is irritating to the eyes.
Picaridin or KBR 3023 was introduced on the repellent
market in Europe in the 1990s by Bayerand in 2005 in
the United States. It is derived from piperidine, and its che-
mical name is 2(2-hydroxyethyl)-1piperidinecarboxylic acid
1-methylpropyl ester. Piperidine is claimed to be as effective
as DEET. It is odorless, is not greasy, and does not damage
plastics or fabrics (Katz et al. 2008). For a short exposure,
picaridin 30% is safe for children under the age of 12 with
two daily applications. In children 13–17 years old and
adults, three daily applications of picaridin 30% is consid-
ered to be safe (PPAV 2011). A formulation of 20% picaridin
provides 8–10 h of protection (Katz et al. 2008, Strickman
et al. 2009), but skin allergy has been reported (Corazza et al.
Characteristics of plant-derived products: Essential oils
An essential oil is a fragrance obtained from a raw botanical
material. Essential oils are rapidly absorbed by the lungs, skin,
and digestive tract. These extracts are complex mixtures
containing mainly terpenoids (geraniol, citronellol, nootka-
tone) and less frequently aromatic compounds (eugenol,
vanillin) (Strickman et al. 2009). Natural products can be a
priori safer for human use and can provide an ecological ad-
vantage compared to nondegradable compounds such as
DEET. However, they can be toxic; some of them are skin
irritants and can contain carcinogens such as methyl eugenol
(Strickman et al. 2009). The majority of these natural products
active against ticks are terpenoids (Bissinger and Roe 2010).
Plants regularly mentioned in the scientific literature are
lemongrass (Cymbopogon nardus, C. excavatus martinii), cedar
(Chamaecyparis nootkatensis and Juniper virginiana), eucalyptus
(Eucalyptus maculata), geranium (Pelargonium reniforme), mint
(Mentha piperita), lavender (Lavandula augustifolia), lemon-
scented gum (Corymbia citriodora), soybeans (Neonotonia
wightii), and wild tomato (Lycopersicon hirsutum) (Choochote
et al. 2007, Strickman et al. 2009, Bissinger and Roe 2010)
(Table 2). Vanillin is often added to the formulations of es-
sential oils to increase their repellent activity, by reducing the
evaporation process on the skin. Some fixatives such as gen-
apol (10%) and polyethylene glycol (10%) are also used (Amer
and Mehlhorn 2006).
Several aspects complicate the choice of an effective plant-
derived repellent. A wide variety of products can be found
around the world, and a comprehensive list is difficult to es-
tablish. According to the geographical and botanical origin of
the plant and the extraction technique used, the composition
of the essential oil can vary greatly. Environmental factors
such as sunlight and humidity can strongly affect the com-
position. Because most of these products have not been tested
for their effectiveness in reliable assays, their efficacy should
be regarded with some skepticism.
Comparative Studies on the Efficacy of Repellents
Comparative studies have been performed either as in vitro
assays or on volunteers in laboratories or in the field in dif-
ferent areas of the world. Most of these studies were done
on mosquitoes with the aim of decreasing the incidence of
malaria. However, some of them have been conducted to
assess specifically the effectiveness of repellents on ticks. Al-
though soft ticks also transmit certain tick-borne disease
agents (for example, relapsing fever borreliae), very few data
are available to confirm the efficacy of repellents against these
ticks. An old study reports partial protection against Argas
persicus (Kumar et al. 1992). In a review of the literature,
Strickman et al. (2009) declare no protection at all of DEET
against soft ticks.
DEET is the most often tested on hard ticks. Against Am-
blyomma hebraeum, the principal vector of Rickettsia africae,
different concentrations (19.5%, 31.6%, 80%) of DEET were
tested using the human ‘‘finger tip’’ bioassay. Less than 50%
repellency was provided after 4 h for these three products
( Jensenius et al. 2005). When a topically applied 20% lotion of
DEET was compared to the efficacy of picaridin (KBR 3023) at
20% in similar conditions against Amblyomma, DEET pro-
tected for 2 h whereas picaridin protected only for 1 h (Pre-
torius et al. 2003). Comparing three repellents, 33% DEET,
20% picaridin, and 10% IR3535, applied onto the ankles of
volunteers in the laboratory, it was shown that A. americanum
can be repelled for several hours. Formulations with at least
20% ingredient were highly effective because only 10% of the
tested ticks crossed the treated area during the 12 h testing
period (Carroll et al. 2010). Working under field conditions in
Switzerland, Staub et al. (2002) evaluated the effectiveness of a
spray containing 15% of either DEET or EBAAP (IR3535
forestry workers. The repellent effect on I. ricinus was mod-
erately active, with 40% effectiveness against ticks whatever
the molecule tested, when applied under everyday conditions
for a period of 5 months. Overall, IR3535 is more efficient
against ticks than DEET (Strickman et al. 2009). To improve
the efficacy of synthetic repellents, different formulations
were tested. DEET in alcoholic solution or liposomal prepa-
rations of DEET (LIPODEET) and SS220 (Morpel 220) were
applied on rabbits to repel A. americanum and Dermacentor
variabilis. The liposomal preparation of DEET was the most
efficient for repelling both tick species, with no tick binding
to rabbit ears for up to 72 h after application (Salafsky et al.
2000). SS220 also seems to be very efficient against hard
ticks (Carroll et al. 2005, Carroll et al. 2008).
Essential oils and plant extracts represent alternatives to
synthetic molecules. Schwantes et al. (2008) compared the
efficacy of different formulations containing 10% of dodeca-
noic acid (DDA) on different stages of I. ricinus. DDA is a
carboxylic acid derived from coconut oil or palm kernel oil.
Using the moving object (MO) bioassay, it showed an effi-
ciency (80–100% repellency) of 6 h with 10% DDA compared
to the reference repellent picaridin. Bissinger et al. (2009)
evaluated the effectiveness of BioUD
(11-carbon methyl ke-
tone, 2-undecanone), an active ingredient derived from wild
tomato plants, to an equivalent repellency of 98.11% DEET
against A. americanum, D. variabilis, and Ixodes scapularis.
Tested in the laboratory using filter paper surfaces impreg-
nated and not impregnated with repellent, BioUD
better repellency than DEET on A. americanum and I. scapu-
laris. No difference of efficacy was observed between the
two products on D. variabilis. The active compound isolated
from the essential oil of Catmint, (Nepeta cataria), dihy-
dronepetalactone, was effective against I. scapularis in laboratory
testing using human subjects (Feaster et al. 2009). Similarly, the
active compound isolongifolenone, a sesquiterpene isolated
from the pine tree, was effective against Ixodes in laboratory
Systemic repellents like garlic extract are ideal because of
their low cost and because their impact on the environment
would be negligible. A study was conducted with garlic as a
potential repellent against ticks. This study, conducted in the
Swedish army, shows an effect of garlic on ticks with a de-
crease of tick bites in people who consumed garlic versus
placebo (Stjernberg and Berglund 2001). However, the
methodology of this study has been criticized (Katz et al.
2008). In addition, adverse effects such as allergic reactions
and alteration of coagulation have been described in certain
patients (Borrelli et al. 2007).
Acaricide-treated clothing to avoid tick bites
The first impregnation of clothing started during the Sec-
ond World War with repellents developed by the US Army.
DMP, benzyl benzoate, and M-1960 (a cocktail of different
molecules) were tested against trombiculids (a prostigmatic
mite, vector of scrub typhus), mosquitoes, and ticks (McCain
and Leach 2007). In the 1960s, jackets impregnated with DEET
or other repellents were tested successfully. DEET resisted
washing better, lasted longer on fabrics, and seemed to be
more efficient against certain ticks, such as A. americanum,D.
variabilis, and I. scapularis (Schreck et al. 1986, Lane 1989,
Evans et al. 1990). In the 1990s, DEET was supplanted by
permethrin in clothing impregnation that was more resistant
to washing.
Permethrin is a synthetic pyrethroid first marketed in
1973. It acts as a repellent and as an insecticide and is very
active against ticks (Katz et al. 2008). Permethrin can be
applied to clothing, but it should not be applied to skin to
protect from tick bite (Bissinger and Roe 2010). Most studies
of permethrin were first conducted in the 1980s on I. scapu-
laris in the eastern United States. Whether applied to clothing
as an aerosol spray or as an impregnant, permethrin pro-
vided excellent protection from tick bites and was signifi-
cantly more effective than the extended-duration DEET
formulation. The first study exploring the effect of per-
methrin on the main European vector tick I. ricinus took
place in 1997 (Romi et al. 1997). This study, conducted in a
laboratory, confirmed the potential protection conferred by
permethrin against European ticks, but also the negative
impact of repetitive washings on impregnated fabrics. Most
studies conducted thereafter in Europe were performed with
long-lasting impregnated fabrics developed for the US
Army. A field study conducted in France assessed the pro-
tection against D. marginatus tick bites conferred by the long-
lasting permethrin-impregnated battle dress used overseas
by French forces (Ho-Pun-Cheung et al. 1999). In the group
wearing impregnated uniforms, 15% of soldiers reported at
least a tick bite against 26% in the group wearing non-
impregnated uniforms. According to the authors, the num-
ber of tick attachments was significantly lower in soldiers
with impregnated uniforms. Faulde et al. (2003) assessed the
contact toxicity and residual activity of different permethrin-
based fabric impregnation methods against wild nymphal
I. ricinus. A long-lasting polymer-coating impregnation
method was compared to two ‘‘dipping methods,’’ Peri-
10 used by the UK army and IARTF used by the US
forces. Before washing treated fabrics, the knockdown effect
of the polymer-coating method was significantly higher than
the IARFT and Peripel
10 dipping methods. After 100
launderings, the knockdown activity remaining in fabrics
treated by the UTEXBEL method was comparable to the re-
sults obtained after 20 launderings with Peripel
10 and after
28 launderings with IARFT. This laboratory study on long-
lasting impregnated fabrics was followed by a field study
that confirmed the excellent efficacy of this tissue prepara-
tion in the prevention of tick-borne diseases (Faulde et al.
2008). Long-lasting impregnated clothing is also available in
the United States and in Europe for outdoor workers and
travellers. However, few studies are available to assess their
efficacy to protect against tick bites. A recent study com-
pared nontreated summer-weight clothing to summer-
weight clothing treated by different methods of permethrin
impregnation (home-made or factory-based). Whatever
clothing impregnation method used, significant protective
benefits were shown (3.4 times) compared to nontreated
outfits against laboratory-reared I. scapularis nymphs (Miller
et al. 2011). Another study was conducted with outdoor
workers in the United States and pointed out the efficiency of
factory-treated clothing with permethrin versus untreated
clothing to avoid tick bites (Vaughan et al. 2011).
The dermal absorption of permethrin has been demon-
strated, and different models have been proposed to assess it
(Hughes and Edwards 2010, Ross et al. 2011). This risk has
been evaluated (especially after the first Gulf War) for
manual and factory long-lasting impregnation as well as its
effect when combined with DEET (Appel et al. 2008, Ross-
bach et al. 2010). Because permethrin is toxic for the envi-
ronment, long-lasting factory-impregnated clothing should
be preferred.
With the progress of long-lasting impregnation techniques
and with the increase of pyrethroid resistance, alternatives to
permethrin have been studied. Studies were conducted with
DEET, KBR 3023, IR3535, or new natural compounds (plant-
derived) such as limoneme, 2-undecanone, essentials oils of
lemon, eucalyptus, geranium, lavender, nootkatone, carva-
crol, elemol, amaryllis oil, etc. ( Jaenson et al. 2006, Bissinger
et al. 2009, Zhang et al. 2009, Carroll et al. 2010, Carroll et al.
2011b, Jordan et al. 2012). New formulations of DEET (e.g.,
microencapsulation) have also been developed that reduce
the volatility of the molecule to increase the resistance to
washing while maintaining sufficient bioavailability. Fabrics
impregnated with DEET or IR3535 have been tested in the
laboratory against I. ricinus nymphs. When nymphs were
constantly exposed to impregnated fabrics, knockdown and
killing effects were observed. This work, which was con-
ducted with impregnated bed nets, suggests that impregna-
tion of clothing with synthetic repellents protects against ticks
(Faulde et al. 2010). Nevertheless, the effect of repeated
launderings remains to be tested.
Concerning natural compounds (extracts or commercial
products) in clothing impregnation against ticks, different
studies have been carried out to assess the protection against
D. variabilis,A. americanum,andI. scapularis. Laboratory
studies were conducted with elemol, amaryllis oil, nooka-
tone, carvacol, and 2-undecanone. Elemol and amaryllis oil
were as effective as DEET in repelling A. americanum and
I. scapularis, but the sensitivity of the two species varied ac-
cording to the amount of product (Carroll et al. 2011b).
(2-undecanone, derived from tomato plant) tested
was found to be as effective as DEET on clothing in repelling
D. variabilis;BioUD
compared to commercially available
repellents was as effective as 20% DEET and more effective
than IR3535 in repelling D. variabilis and A. americanum
(Bissinger et al. 2009, Kimps et al. 2011).
Currently, only permethrin solutions for spraying or dip-
ping and some long-lasting fabrics are commercially available
to protect people from tick bites. Self-impregnation with
permethrin has clearly proven its efficacy in tick bite pre-
vention, but it can expose people to high concentrations of the
product. For safety reasons, long-lasting impregnated cloth-
ing is recommended, although most of the studies assessing
its efficacy were conducted in the army. New products and
impregnation technologies should lead to better prevention of
tick bites (Pohlit et al. 2011, Solomon et al. 2012).
An integrated approach to avoid tick bites and tick-trans-
mitted pathogens is necessary. This includes the use of both
protective clothing and tick repellents, checking the entire
body daily if exposed to ticks, and prompt removal of at-
tached ticks before transmission of infection may occur
(Wormser et al. 2006, Piesman and Eisen 2008, PPAV 2011).
Concerning the use of repellents, more reliable assays specific
for ticks are necessary with clear technical guidelines to avoid
high variations in results (Dautel et al. 2013). All repellents
must be applied on skin or on clothing according to the in-
structions of the manufacturers and according to official
agencies, which have fixed precise rules for their use. With the
increasing incidence of arthropod-borne diseases in different
areas of the world, new molecules are needed to prevent the
transmission of pathogens.
N. Boulanger thanks the Fulbright-Re
´gion Alsace founda-
tion and the Monahan foundation for their financial support.
Author Disclosure Statement
There are no conflicts of interest.
Amer A, Mehlhorn H. Repellency effect of forty-one essential
oils against Aedes,Anopheles, and Culex mosquitoes. Parasitol
Res 2006; 99:78–90.
Appel KE, Gundert-Remy U, Fischer H, Faulde M, et al. Risk
assessment of Bundeswehr (German Federal Armed Forces)
permethrin-impregnated battle dress uniforms (BDU). Int J
Hyg Environ Health 2008; 211:88–104.
Bissinger BW, Roe RM. Tick repellents: Past, present and future.
Pestic Biochem Physiol 2010; 96:63–79.
Bissinger BW, Apperson CS, Sonenshine DE, Watson DW, et al.
Efficacy of the new repellent BioUD
against three species of
ticks. Exp Appl Acarol 2009; 48:239–250.
Bissinger BW, Apperson CS, Watson DW, Arellano C, et al.
Novel field assays and the comparative repellency of
BioUD(), DEET and permethrin against Amblyomma amer-
icanum. Med Vet Entomol 2011; 25:217–226.
Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): Ad-
verse effects and drug interactions in humans. Mol Nutr Food
Res. 2007; 51:1386–1397.
Carroll JF, Benante JP, Klun JA, White CE, et al. Twelve-hour
duration testing of cream formulations of three repellents
against Amblyomma americanum. Med Vet Entomol 1998;
Carroll JF, Solberg VB, Klun JA, Kramer M, et al. Comparative
activity of DEET and AI3-37220 repellents against the ticks
Ixodes scapularis and Amblyomma americanum (Acari: Ix-
odidae) in laboratory bioassays. J Med Entomol 2004; 41:
Carroll JF, Klun JA, Debboun M. Repellency of DEET and SS220
applied to skin involves olfactory sensing by two species of
ticks. Med Vet Entomol 2005; 19:101–106.
Carroll JF, Cantrell CL, Klun JA, Kramer M. Repellency of two
terpenoid compounds from Callicarpa americana (Lamiaceae)
against Ixodes scapularis and Amblyomma americanum ticks. Exp
Appl Acarol 2007; 41:215–224.
Carroll SP. Prolonged efficacy of IR3535 repellents against
mosquitoes and blacklegged ticks in North America. J Med
Entomol 2008; 45:706–714.
Carroll JF, Benante JP, Kramer M, Lohmeyer KH, et al. For-
mulations of DEET, picaridine, and IR3535 applied to skin
repel nymphs of the lone star tick (Acari: Ixodidae) for 12
hours. J Med Entomol 2010; 47:699–704.
Carroll JF, Zhang A, Kramer F. Using Lone Star Ticks, Amblyomma
americanum (Acari, ixodidae) in in vitro laboratory bioas-
says with repellents: Dimensions, duration, and variability.
In: Paluch G, Coats J, eds. Recent Developments in Invertebrate
Repellents. Washington DC: ACS Symposium Series, American
Chemical Society, 2011a:97–120
Carroll JF, Tabanca N, Kramer M, Elejalde NM, et al. Essential
oils of Cupressus funebris,Juniperus communis, and J. chinensis
(Cupressaceae) as repellents against ticks (Acari: Ixodidae)
and mosquitoes (Diptera: Culicidae) and as toxicants against
mosquitoes. J Vector Ecol 2011b; 36:258–268.
Choochote W, Chaithong U, Kamsuk K, Jitpakdi A, et al. Re-
pellent activity of selected essential oils against Aedes aegypti.
Fitoterapia 2007; 78:359–364.
Corazza M, Borghi A, Zampino MR, Virgili A. Allergic contact
dermatitis due to an insect repellent: Double sensitization to
picaridin and methyl glucosedioleate. Acta Derm Venereol
2005; 85:264–265.
Dautel H, Kahl O, Siems K, Oppenrieder M, et al. A novel test
system for detection of tick repellents. Entomol Exp Appl
1999; 91:431–441.
Dautel H. Test systems for tick repellents. Mini Review. Int J
Med Microbiol 2004; 293(S37):182–188.
Dautel H, Dippel C, Werkhausen A, Diller R. Efficacy testing of
several Ixodes ricinus tick repellents: Different results with
different assays. Ticks Tick Borne Dis 2013; 4:256–263.
Debboun M, Strickman D. Insect repellents and associated per-
sonal protection for a reduction in human disease. Med Vet
Entomol 2013; 27:1–9.
Dietrich G, Dolan MC, Peralta-Cruz J, Schmidt J, et al. Repellent
activity of fractionated compounds from Chamaecyparis noot-
katensis essential oil against nymphal Ixodes scapularis (Acari:
Ixodidae). J Med Entomol 2006; 43:957–961.
El-Seedi HR, Khalil NS, Azeem M, Taher EA, et al. Chemical
composition and repellency of essential oils from four me-
dicinal plants against Ixodes ricinus nymphs (Acari: Ixodidae).
J Med Entomol 2012; 49:1067–1075.
Evans SR, Korch GW, Lawson MA. Comparative field evalua-
tion of permethrin and DEET-treated military uniforms
for personal protection against ticks. J Med Entomol 1990;
´tico T, Labruna MB, Verderane MP, De Resende BD, et al.
Repellent efficacy of formic acid and the abdominal secretion of
carpenter ants (Hymenoptera: Foricidae) against Amblyomma
ticks (Acari: Ixodidae). J Med Entomol 2007; 44:718–721.
Faulde MK, Uedelhoven WM, Robbins, RG. Contact toxicity and
residual activity of different permethrin-based fabric impreg-
nation methods for Aedes aegypti (Diptera: Culicidae), Ixodes
ricinus (Acari: Ixodidae), and Lepisma saccharina (Thysanura:
Lepismatidae). J Med Entomol 2003; 40:935–941.
Faulde M, Scharninghausen J, Tisch M. Preventive effect of
permethrin impregnated clothing to Ixodes ricinus ticks and
associated Borrelia burgdorferi s.l. in Germany. Int J Med Mi-
crobiol 2008; 298:321–324.
Faulde MK, Albiez G, Nehring O. Insecticidal, acaricidal and
repellent effects of DEET- and IR3535-impregnated bed nets
using a novel long-lasting polymer-coating technique. Para-
sitol Res 2010; 106:957–965.
Feaster JE, Scialdone MA, Todd RG, Gonzalez YI, et al. Dihy-
dronepetalactones deter feeding activity by mosquitoes, stable
flies, and deer ticks. J Med Entomol 2009; 46:832–840.
Frischknecht F. The skin as interface in the transmission of ar-
thropod-borne pathogens. Cell Microbiol 2007; 9:1630–1640.
Gardulf A, Wohlfahrt I, Gustafson R. A prospective cross-over
field trial shows protection of lemon eucalyptus extract
against tick bites. J Med Entomol 2004;41:1064–1067.
Ho-Pun-Cheung T, Lamarque D, Josse R, Perez-Eid C, et al.
Protective effect of clothing impregnated with permethrin
against D. reticulatus and D. marginatus in an open biotope of
central western France. Bull Soc Pathol Exot 1999; 92:337–340.
Hughes MF, Edwards BC. In vitro dermal absorption of pyre-
throid pesticides in human and rat skin. Toxicol Appl Phar-
macol 2010; 246:29–37.
Jaenson TGT, Pa
˚lsson K, Borg-Karlsson A-K. Evaluation of ex-
tracts and oils of tick-repellent plants from Sweden. Med Vet
Entomol 2005; 19;345–352.
Jaenson TGT, Garboui S, Pa
˚lson K. Repellency of oils of Lemon
Eucalyptus, Geranium, and Lavender and the mosquito re-
pellent MyggA natural to Ixodes ricinus (Acari: Ixodidae) in the
laboratory and field. J Med Entomol 2006; 43:731–736.
Jensenius M, Pretorius AM, Clarke F, Myrvang B. Repellent ef-
ficacy of four commercial DEET lotions against Amblyomma
hebraeum (Acari: Ixodidae), the principal vector of Rickettsia
africae in southern Africa. Trans R Soc Trop Med Hyg 2005;
Jordan RA, Schulze TL, Dolan MC. Efficacy of plant-derived and
synthetic compounds on clothing as repellents against Ixodes
scapularis and Amblyomma americanum (Acari: Ixodidae).
J Med Entomol 2012; 49:101–106.
Kaaya GP, Mwangi EN, Malonza MM. Acaricidal activity of
Margarita discoidea (Euphorbiaceae) plant extracts against the
ticks Rhipicephalus appendiculatus and Amblyomma variegatum
(Ixodidae). Internat. J Acarol 1995; 21:123–129.
Kasting GB, Bhatt VD, Speaker TJ. Microencapsulation decreases
the skin absorption of N,N-diethyl-m-toluamide (DEET).
Toxicol In Vitro 2008; 22:548–552.
Katz TM, Miller JH, Hebert AA. Insect repellents: Historical
perspectives and new developments. J Am Acad Dermatol
2008; 58:865–871.
Kimps NW, Bissinger BW, Apperson CS, Sonenshine DE, et al.
First report of the repellency of 2-tridecanone against ticks.
Med Vet Entomol 2011: 25;202–208.
Kocan KM, de la Fuente J, Blouin EF. Advances toward under-
standing the molecular biology of the Anaplasma-tick interface.
Front Biosci 2008; 13:7032–7045.
Kumar S, Prakash S, Kaushik MP, Rao KM. Comparative ac-
tivity of three repellents against the ticks Rhipicephalus san-
guineus and Argas persicus. Med Vet Entomol 1992; 6:47–50.
Lane RS. Treatment of clothing with a permethrin spray for per-
sonal protection against the Western Black-Legged Tick, Ixodes
pacificus (Acari: Ixodidae). Exp Appl Acarol 1989; 6:343–352.
Mansfield KL, Johnson N, Phipps LP, Stephenson JR, et al. Tick-
borne encephalitis virus—a review of an emerging zoonosis.
J Gen Virol 2009; 90:1781–1794.
McCain WC, Leach GJ. Repellents used in fabric: The experience
of the U.S. military. In: Insects Repellents Principles, Methods and
Uses, chapter XIII. Boca Raton, FL: CRC/Taylor & Francis,
Mehlhorn H. Encyclopedic Reference of Parasitology,2
ed. Berlin,
Heidelberg: Spinger-Verlag, 2001.
Miller NJ, Rainone EE, Dyer MC, Gonza
´lez ML, et al. Tick bite
protection with permethrin-treated summer-weight clothing. J
Med Entomol 2011; 48:327–333.
Mwangi EN, Essuman S, Kaaya GP, Nyandat E, et al. Repellence
of the tick Rhipicephalus appendiculatus by the grass Melinis
minutiflora. Trop Anim Hlth Prod 1995; 27:211–216.
Ndungu M, Lwande W, Hassanali A, Moreka L, Chhabra SC.
Cleome monophylla essential oil and its constituents as tick
(Rhipicephalus appendiculatus) and maize weevil (Sitophilus
zeamais) repellents. Ent Exp Appl 1995; 76:217–222.
Piesman J, Eisen L. Prevention of tick-borne diseases. Annu Rev
Entomol 2008; 53:323–343.
Pohlit AM, Rezende AR, Lopes Baldin EL, et al. Plant extracts,
isolated phytochemicals, and plant-derived agents which are
lethal to arthropod vectors of human tropical diseases—a re-
view. Planta Med 2011; 77:618–630.
PPAV Working Groups. Personal protection against biting in-
sects and ticks. Parasite 2011; 18:93–111.
Pretorius A-M, Jensenius M, Clarke F, Ringertz SH. Repellent
efficacy of DEET and KBR 3023 against Amblyomma hebraeum
(Acari: Ixodidae). J Med Entomol 2003; 40:245–248.
Proniuk S, Liederer BM, Dixon SE, Rein JA, et al. Topical for-
mulation studies with DEET (N,N-diethyl-3-methylbenza-
mide) and cyclodextrins. J Pharm Sci 2002; 91:101–110.
Romi R, Peragallo M, Sarnicola G, Dommarco R. Impregnation
of uniforms with permethrin as a mean of protection of
working personnel exposed to contact with hematophagous
arthropods. Ann Ig 1997; 9:313–319.
Ross JH, Reifenrath WG, Driver JH. Estimation of the percuta-
neous absorption of permethrin in humans using the paral-
lelogram method. J Toxicol Environ Health 2011; 74:351–363.
Rossbach B, Appel KE, Mross KG, Letzel S. Uptake of permethrin
from impregnated clothing. Toxicol Lett 2010; 192:50–55.
Salafsky B, He YX, Li J, Shibuya T, et al. Short report: Study on
the efficacy of a new long-acting formulation of N, N-diethyl-
m-toluamide (DEET) for the prevention of tick attachment.
Am J Trop Med Hyg 2000; 62:169–172.
Schreck CE, Snoddy EL, Spielman A. Pressurized sprays of per-
methrin or DEET on military clothing for personal protection
against Ixodes dammini (Acari: Ixodidae). J Med Entomol 1986;
Schreck CE, Fish D, McGovern TP. Activity of repellents applied
to skin for protection against Amblyomma americanum and
Ixodes scapularis ticks (Acari: Ixodidae). J Am Mosqu Control
Assoc 1995; 11:136–140.
Schwan TG, Piesman J. Vector interactions and molecular ad-
aptations of lyme disease and relapsing fever spirochetes as-
sociated with transmission by ticks. Emerg Infect Dis 2002;
Schwantes U, Dautel H, Jung G. Prevention of infectious tick-
borne diseases in humans: Comparative studies of the re-
pellency of different dodecanoic acid-formulations against
Ixodes ricinus ticks (Acari: Ixodidae). Parasit Vectors 2008;
Solberg VB, Klein TA, McPherson KR, Bradford BA, et al. Field
evaluation of DEET and a piperidine repellent (AI3-37220)
against Amblyomma americanum (Acari:Ixodidae). J Med En-
tomol 1995; 32:870–875.
Solomon B, Sahle FF, Gebre-Mariam T, Asres K, et al. Micro-
encapsulation of citronella oil for mosquito-repellent applica-
tion: Formulation and in vitro permeation studies. Eur J
Pharm Biopharm 2012; 80:61–66.
Sonenshine DE. The mouthparts and foregut: Capitulum, phar-
ynx and esophagus. In: Biology of Ticks. New York: Oxford
University Press, 1991.
Staub D, Debrunner M, Amsler L, Steffen R. Effectiveness of a
repellent containing DEET and EBAAP for preventing tick
bites. Wilderness Environ Med 2002; 13:12–20.
Stjernberg L, Berglund J. Garlic as a tick repellent. JAMA 2001;
Strickman D, Frances SP, Debboun M. Prevention of Bug Bites,
Stings and Disease. USA: Oxford University Press, 2009.
Vaughan MF, Meshnick SR. Pilot study assessing the effective-
ness of long-lasting permethrin-impregnated clothing for the
prevention of tick bites. Vector Borne Zoonotic Dis 2011;
Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, et al. The
clinical assessment, treatment, and prevention of lyme disease,
human granulocytic anaplasmosis, and babesiosis: Clinical
practice guidelines by the Infectious Diseases Society of
America. Clin Infect Dis 2006; 43:1089–1134.
Zhang A, Klun JA, Wang S, Carroll JF, Debboun M. Iso-
longifolenone: A novel sesquiterpene repellent of ticks and
mosquitoes. J Med Entomol 2009; 46:100–106.
Address correspondence to:
Nathalie Boulanger
Institute of Bacteriology
University of Strasbourg
3 rue Koeberle
Strasbourg 67 000
... An important difference between these two subphyla is that Hexapoda have odorant, gustatory, and ionotropic receptors, whereas Chelicerata only have gustatory and ionotropic receptors 29-31 . Intriguingly, studies have found that many commercial insect repellents like DEET, picaridin, or IR3535, are effective repellents on both ticks and mosquitoes 32,33 . This raises the question if mosquitoes and ticks, two groups of organisms with different sensory organs and receptor proteins, will be repelled by the same active ingredients from the EPA 25(b) list. ...
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Cases of mosquito- and tick-borne diseases are rising worldwide. Repellent products can protect individual users from being infected by such diseases. In a previous study, we identified five essential oils that display long-distance mosquito repellency using a Y-tube olfactometer assay. In the current study, the contact repellent efficacy of 20 active ingredients from the Environmental Protection Agency’s (EPA) Minimum Risk Pesticides list were tested using Aedes aegypti and Ixodes scapularis. We utilized an arm-in-cage assay to measure complete protection time from mosquito bites for these active ingredients. To measure tick repellency, we used an EPA-recommended procedure to measure the complete protection time from tick crossings. We found that of the 20 ingredients tested, 10% v/v lotion emulsions with clove oil or cinnamon oil provided the longest protection from both mosquito bites and tick crossings. We conclude that in a 10% v/v emulsion, specific active ingredients from the EPA Minimum Risk Pesticides list can provide complete protection from mosquito bites and tick crossings for longer than one hour.
... In Europe, the castor bean tick, Ixodes ricinus can transmit pathogens leading to the development of tick-borne diseases such as Lyme borreliosis or tick-borne encephalitis (Barbour and Benach, 2019;Cardenas-de la Garza et al., 2019;Lindquist, 2008;Rizzoli et al., 2011). To avoid tick bites, repellents (natural or synthetic substances that causes ticks to either avoid or leave the host, stopping them from attaching, biting, or feeding) are used to prevent animal-vector contact (Pages et al., 2014). Thus, the term repellency which was classically used to describe the effects of a substance that causes a flying arthropod, such as mosquitoes, to make oriented movements away from its source, suggests for ticks, a range of behavioral responses (Halos et al., 2012). ...
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... Picaridin (icaridine, 1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropylester), a cyclic amine and a member of the piperidine chemical family, is viewed as a synthetic, broad-spectrum arthropod repellent [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The repellent and deterrent activities of picaridin have been previously demonstrated to involve olfactory sensing in mosquitoes and ticks, via their interactions with odorant receptor proteins residing in neurons [17][18][19][20][21][22]. ...
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Picaridin (icaridin), a member of the piperidine chemical family, is a broad-spectrum arthropod repellent. Its actions have been largely thought to be due to its interaction with odorant receptor proteins. However, to our knowledge, to what extent the presence of picaridin can modify the magnitude, gating, and/or the strength of voltage-dependent hysteresis (Hys(V)) of plasmalemmal ionic currents, such as, voltage-gated Na+ current [INa], has not been entirely explored. In GH3 pituitary tumor cells, we demonstrated that with exposure to picaridin the transient (INa(T)) and late (INa(L)) components of voltage-gated Na+ current (INa) were differentially stimulated with effective EC50’s of 32.7 and 2.8 μM, respectively. Upon cell exposure to it, the steady-state current versus voltage relationship INa(T) was shifted to more hyperpolarized potentials. Moreover, its presence caused a rightward shift in the midpoint for the steady-state inactivate curve of the current. The cumulative inhibition of INa(T) induced during repetitive stimuli became retarded during its exposure. The recovery time course from the INa block elicited, following the conditioning pulse stimulation, was satisfactorily fitted by two exponential processes. Moreover, the fast and slow time constants of recovery from the INa block by the same conditioning protocol were noticeably increased in the presence of picaridin. However, the fraction in fast or slow component of recovery time course was, respectively, increased or decreased with an increase in picaridin concentrations. The Hys(V)’s strength of persistent INa (INa(P)), responding to triangular ramp voltage, was also enhanced during cell exposure to picaridin. The magnitude of resurgent INa (INa(R)) was raised in its presence. Picaritin-induced increases of INa(P) or INa(R) intrinsically in GH3 cells could be attenuated by further addition of ranolazine. The predictions of molecular docking also disclosed that there are possible interactions of the picaridin molecule with the hNaV1.7 channel. Taken literally, the stimulation of INa exerted by the exposure to picaridin is expected to exert impacts on the functional activities residing in electrically excitable cells.
... NEG = Untreated drag, ACE = Acetone only treated drags, DEET = N, N-diethyl-m-toluamide, CCC = citronellyl cyclobutane carboxylate, EPC = Ethyl perillyl carbonate, GI = Geranyl Isovalerate. three compounds may have been reached at a concentration of 0.16 mg/cm 2 and higher concentrations would not yield additional repellency benefits (Pages et al. 2014, Diaz 2016, Meng et al. 2016. However, HiC results may have been impacted by the low density of nymphs in July and a larger sample size may provide different insight into the effectiveness of the repellents. ...
Three compounds synthetically-derived from botanicals sources, ethyl perillyl carbonate, geranyl isovalerate, and citronellyl cyclobutane carboxylate, were tested for repellent activity against Ixodes scapularis Say in a field trial. Tick drags were treated with the compounds or with N, N-diethyl-m-toluamide (DEET) at high (0.25 mg/cm2) or low (0.16 mg/cm2) concentrations. Negative controls included untreated drags and drags treated with acetone, the carrier for all repellents. Freshly treated drags (within 20 min) were used to collect I. scapularis ticks at a county park in Wisconsin. To assess effectiveness, we measured tick encounter rates, detachment rate, and time to detachment. None of the repellent treatments, including DEET, resulted in significantly fewer encounters compared to both control treatments. However, the percentage of ticks that detached within 3 min was significantly higher on drags treated with repellents compared to controls. DEET was the most effective, repelling 69.7–87% of ticks by 3 min, but the effectiveness of the three test compounds was still high, with 42–87% of ticks detaching by 3 min. For time to detachment, there were no significant differences between DEET and the three test compounds. We conclude that these synthetically-derived repellents were effective against I. scapularis in a field trial and could be viable alternatives to DEET.
In the context of complex public health challenges led by interdependent changes such as climate change, biodiversity loss, and resistance to treatment, it is important to mobilize methods that guide us to generate innovative interventions in a context of uncertainty and unknown. Here, we mobilized the concept-knowledge (CK) design theory to identify innovative, cross-sectoral, and cross-disciplinary research and design programs that address the challenges posed by tick-borne Lyme disease in France, which is of growing importance in the French public health and healthcare systems. Within the CK methodological framework, we developed an iterative approach based on literature analysis, expert interviews, analysis of active French research projects, and work with CK experts to contribute to design “an action plan against Lyme disease.” We produced a CK diagram that highlights innovative concepts that could be addressed in research projects. The outcome is discussed within four areas: (i) effectiveness; (ii) environmental sustainability in prevention actions; (iii) the promotion of constructive involvement of citizens in Lyme challenges; and (iv) the development of care protocols for chronic conditions with an unknown diagnosis. Altogether, our analysis questioned the health targets ranging from population to ecosystem, the citizen involvement, and the patient consideration. This means integrating social and ecological science, as well as the multidisciplinary medical patient journey, from the start. CK theory is a promising framework to assist public health professionals in designing programs for complex yet urgent contexts, where research and data collection are still not sufficient to provide clear guidance.
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L’augmentation des populations de tiques dans le monde, due au changement climatique et au développement de résistance aux acaricides, met en évidence le besoin de nouvelles méthodes de contrôle. La caractérisation de nouvelles cibles moléculaires aux acaricides est donc nécessaire. Les récepteurs à l’acétylcholine de type nicotinique (ou nAChRs) sont des cibles pour les pesticides (comme les néonicotinoïdes) chez les arthropodes et sont peu étudiés chez la tique. Ce sont des protéines transmembranaires formées de cinq sous-unités et qui sont impliquées dans la neurotransmission synaptique rapide. Les objectifs de cette thèse sont de caractériser les profils pharmacologiques des nAChRs neuronaux chez la tique Ixodes ricinus et d’identifier de nouvelles molécules acaricides qui pourront être utilisées dans la prévention et la lutte contre les tiques. Pour accomplir ces objectifs de thèse, une nouvelle technique a été mise au point sur cette espèce de tique, la microtransplantation de membranes purifiées provenant du cerveau (ou synganglion) de la tique et leur expression en système hétérologue. Cette technique inédite a permis pour la première fois de caractériser les nAChRs natifs de la tique I. ricinus. Nous avons démontré la sensibilité des nAChRs à différents agonistes (acétylcholine et nicotine), antagonistes (alpha-bungarotoxine et méthyllycaconitine), ainsi que la faible sensibilité à des néonicotinoïdes. Néanmoins, l’utilisation d’un modulateur allostérique positif (le PNU-120596) a permis d’augmenter la sensibilité des nAChRs natifs à ces molécules. De plus, nous avons identifié plusieurs sous-unités de nAChRs chez la tique I. ricinus. En particulier, nous avons réalisé le clonage de sous-unité de nAChRs. En complément de ces études in-vitro, nous avons mené de nouvelles expériences comportementales sur des tiques adultes pour observer l’effet répulsifs de composés. Pour conclure, ces travaux ont mis en évidence la présence de nAChRs au sein du synganglion de la tique I. ricinus. Les résultats obtenus grâce à leur caractérisation moléculaire, électrophysiologique ainsi que l’approche comportementale sont encourageant pour le développement de nouvelles molécules acaricides et répulsives contre I. ricinus.
Since the discovery of the etiological agents of Lyme disease, Borrelia burgdorferi sensu lato (s.l.), many efforts have been undertaken to understand the nature of the pathobiology these pathogens cause in humans. Here we describe the current knowledge of the most important borrelial determinants and factors and how they interact in different ways with soluble host proteins, tissues, and organs at different time points within the multistep infection process. We also describe the specific responses and signaling pathways that are induced by the human host to combat the intruding pathogen. While not a complete list, factors involved in host adaptation, tissue colonization, dissemination, and persistence of Borrelia are addressed, as well as factors playing a key role in immune evasion. Further aspects such as the induction of inflammatory mediators and the role of B and T cells in host responses, as well as the recognition and persistence of spirochetes are also discussed. Despite the huge collection and collation of data within the last two decades, our picture of the pathogenesis of Lyme diseases is still a big puzzle, in which the shape and certain characteristics are visible, but the whole picture is covered with a blurry veil.KeywordsImmune evasionadaptive immunityinnate immunitycomplementvirulence factorshost response
Lyme borreliosis is the most common tick-borne disease in the temperate northern hemisphere. The bacterium responsible for the disease, Borrelia burgdorferi sensu lato (s.l.), occurs predominantly in small mammals and is transmitted by certain species of Ixodes. Long-lasting blood meals for several days are characteristic for this tick species. Deer are one of the preferred hosts of Ixodes adults and therefore contribute substantially to the maintenance of tick populations. Although humans are accidental hosts, Lyme borreliosis represents an important challenge to Public Health. Personal protective measures against tick bite include adequate clothing and the use of repellents. Rapid detachment of the tick after a bite is essential and the bite site must be observed for the possible appearance of clinical symptoms.An integrative approach is required for the control of this zoonotic disease. Rodent reservoirs can be targeted by topical acaricides, oral vaccines against B. burgdorferi, or antibiotic baits. Reduction of deer abundance can be used to suppress tick populations. Effective modifications to make the environment less attractive for ticks include leaf removal, controlled vegetation burning, and lawn mowing. However, the ultimate gold standard to control this disease in humans would be an efficient vaccine, which is still not available.KeywordsLymeZoonosisDeerBorrelia burgdorferi sensu lato Ixodes RepellentsAnthropizationRodentPreventionVaccine
Personal protection measures to prevent human tick encounters from resulting in bites are widely recommended as the first line of defense against health impacts associated with ticks. This includes using repellents, wearing untreated or permethrin-treated protective clothing, and conducting tick checks after coming inside, aided by removing outdoor clothing articles and running them in a dryer on high heat (to kill undetected ticks) and taking a shower/bath (to aid in detecting ticks on the skin). These measures have the benefit of incurring no or low cost, but they need to be used consistently to be most effective. In this paper, I review the level of use (acceptability combined with behavior) of the above-mentioned personal protection measures and their effectiveness to prevent tick bites and tick-borne disease. Studies on the level of use of personal protection measures to prevent tick bites have used different recruitment strategies, focused on different types of respondent populations, employed variable phrasings of survey questions relating to a given personal protection measure, and presented results based on variable frequencies of taking action. This complicates the synthesis of the findings, but the studies collectively indicate that members of the public commonly take action to prevent tick bites, most frequently by wearing untreated protective clothing or conducting tick checks (done routinely by 30 to 70% of respondents in most studies of the public), followed by showering/bathing after being outdoors or using repellents on skin/clothing (15 to 40% range), and with permethrin-treated clothing being the least frequently used tick bite prevention method (<5 to 20% range). A suite of experimental studies has shown that applying repellents or permethrin to coveralls or uniform-style clothing can result in decreased numbers of tick bites, but similar studies are lacking for members of the public wearing summer-weight clothing during normal daily activities. Moreover, a set of case-control and cross-sectional studies have explored associations between use of different personal protection measures to prevent tick bites and Lyme disease or other tick-borne infections. The results are mixed for each personal protection measure, with some studies indicating that regular use of the measure is associated with a reduction in tick-borne disease while other studies found no similar protective effect. One possible interpretation is that these personal protection measures can protect against tick-borne infection but the information gathered to date has not been sufficiently detailed to clarify the circumstances under which protection is achieved, especially with regards to frequency of use, parts of the body being protected, and use of combinations of two or more potentially protective measures. In conclusion, personal protection measures to prevent tick bites are used by the public and merit further study to better understand how they need to be used to have the greatest public health impact.
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The in vitro laboratory bioassay is an important tool in tick repellent discovery and development, with a variety of bioassays used in recent years. Several factors, such as size and configuration of test surfaces and duration of tick exposure, can influence the outcome of bioassays. We tested two tick repellents, N,N-diethyl-3-methyl benzamide (deet) and (-)-isolongifolenone, in seven different bioassays or configurations. All bioassays used ≥4 concentrations of repellent and an ethanol control applied to filter paper against lone star tick nymphs, Amblyomma americanum (L.). Climbing bioassays included a 22 × 1 cm vertical filter paper strip and a 4 × 7 cm vertical filter paper strip plus four modifications of the basic 4 × 7 cm configuration. We used a moving object bioassay (MOB), in which a strip of filter paper treated with test solution was affixed to a rotating heated brass drum and ticks allowed to transfer to the paper. A horizontal bioassay in which ticks were confined between two filter paper discs that had one half treated with repellent was also used. For each bioassay, deet and (-)-isolongifolenone were similarly effective, but in some bioassays ticks were repelled by lower concentrations of both repellents than in other bioassays. The 22 × 1 cm strip proved impractical for regular bioassay use, but showed that a height of 8-9 cm and ~6 min duration were optimal for climbing bioassays. When a loop of treated paper was added to untreated lower portion of the 4 × 7 cm filter paper, as alternative escape for ticks responding to repellents, more ticks were on the loop and lower untreated area of the strip at 10 min (end of the test) than were on the lower untreated area of the basic 4 × 7 cm strip. However, with the ethanol controls more ticks fell from 4 × 7 cm strips with loops than those without loops. Several important behaviors associated with host acquisition (contacting, transferring to and remaining on a moving surface) were recorded in the MOB, but we only found significant differences between treatment and control for the proportion of ticks that transferred to the filter paper and the length of time the ticks remained on paper. The petri dish bioassays lasted longer than other bioassays (2h compared to 10 min for the vertical filter bioassays) and allowed detection of a decline in repellency over time. Individual variation among ticks and fatigue (change in response) in repeatedly tested ticks were assessed in a vertical paper strip bioassay using deet. The responses of ticks tested twice on one day (morning and afternoon) did not differ between tests. However, continued repeated daily testing compromised results. A hiatus of about a week between tests allowed ticks to return to their initial response profiles.
Venoms from scorpions, spiders, centipedes, ants, wasps, and bees can be very poisonous, or induce serious allergic reactions. Blood sucking mites, ticks, lice, bed bugs, kissing bugs, sand flies, biting midges, black flies, mosquitoes, snipe flies, horse flies, tsetse flies, stable flies, and fleas cause irritation. More seriously, some of them can leave behind pathogens that cause serious diseases. This volume presents the full spectrum of methods necessary for prevention of bites and stings from the worldwide variety of bloodsucking and venomous arthropods. The first step is identification of the problem by identifying the bug, knowing where the bug occurs, and deciding whether or not the problem is seriously connected to health problems. The next step is to build the bugs out of the personal environment of the home and its surrounding property. If those methods do not give complete relief, insecticides can sometimes provide the solution. Barriers like screens and doors can at least help when people are indoors. Outside, clothing can make a big difference, especially if repellents are applied to the cloth. The last resort for people exposed to bloodsucking bugs is to use repellents on the skin. This book provides information that will help in choosing the right repellent among the dozens of natural and synthetic products.
Cited By (since 1996):4 , Export Date: 25 April 2013 , Source: Scopus , The following values have no corresponding Zotero field: Author Address: University Medical Center, the Johannes Gutenberg University Mainz, Institute for Occupational, Social, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany Author Address: Federal Institute for Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany Author Address: Bundeswehr Regional Medical Command II, Occupational Medicine, Schloss Oranienstein, 65582 Diez, Germany
A water soluble extract of M. discoidea, an African indigenous plant induced high mortalities in nymphs of both Rhipicephalus appendiculatus, and Amblyomma variegatum and in adult R. appendiculatus, but not in adult A. variegatum. An oil hexane extract from dry wood of this plant was found to be more acaricidal and a 6.25% concentrated extract killed 100% nymphal R. appendiculatus, 100% adult R. appendiculatus and 100% adult A. variegatum when exposed to the extract for 10 min. Application of a 50% concentrated oil extract on rabbit ears caused a complete inhibition of attachment by adult R. appendiculatus and A. variegatum for at least 4 days, and when applied on adult ticks engorging on rabbits, it induced mortalities of 70% and 97% in A. variegatum and R. appendiculatus, respectively. When applied on ticks naturally infesting cattle in the field, the 50% oil extract induced 100% and 50% mortalities in adult R. appendiculatus and A. variegatum, respectively, by 2 days post-application. In adult R. appendiculatus, feeding on cattle the 50% oil extract was found to be as effective as the standard concentration (0.05%) of steladone, a commercial acaricide.
The repellency of the essential oil of the shrub Cleome hirta and of three identified constituents (phytol, (+)-cedrol, n-octacosane) was evaluated against the livestock tick, Rhipicephalus appendiculatus and the maize weevil, Sitophillus zeamais. In a tick climbing repellency bioassay, the oil exhibited repellency which, at the highest dose, was comparable to that of the commercial arthropod repellent N,N-diethyltoluamide (DEET). In a Y-tube olfactometer bioassay, the oil showed higher or comparable repellency against S. zeamais relative to DEET at all the doses tested. The potential of C. hirta in livestock tick and maize weevil control is discussed.