Elsevier

Travel Medicine and Infectious Disease

Volume 11, Issue 6, November–December 2013, Pages 374-411
Travel Medicine and Infectious Disease

Review
The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp. – A literature review

https://doi.org/10.1016/j.tmaid.2013.10.005Get rights and content

Summary

Background

Travellers are confronted with a variety of vector-borne threats. Is one type of repellent effective against all biting vectors? The aim of this review is to examine the literature, up to December 31st, 2012, regarding repellent efficacy.

Methods

We searched PubMed for relevant papers. Repellents of interest were DEET, Icaridin as well as other piperidine-derived products (SS220), Insect Repellent (IR) 3535 (ethyl-butylacetyl-amino-propionat, EBAAP) and plant-derived products, including Citriodora (para-menthane-3,8-diol). As vectors, we considered the mosquito species Anopheles, Aedes and Culex as well as the tick species Ixodes. We selected only studies evaluating the protective efficacy of repellents on human skin.

Results

We reviewed a total of 102 publications.

Repellents were evaluated regarding complete protection time or as percentage efficacy [%] in a time interval. We found no standardized study for tick bite prevention.

Conclusions

Regarding Aedes, DEET at concentration of 20% or more, showed the best efficacy providing up to 10 h protection. Citriodora repellency against this mosquito genus was lower compared to the other products. Also between subspecies a difference could be observed: Ae. aegypti proved more difficult to repel than Ae. Albopictus. Fewer studies have been conducted on mosquito species Anopheles and Culex.

The repellency profile against Anopheles species was similar for the four principal repellents of interest, providing on average 4–10 h of protection.

Culex mosquitoes are easier to repel and all four repellents provided good protection.

Few studies have been conducted on the tick species Ixodes. According to our results, the longest protection against Ixodes scapularis was provided by repellents containing IR3535, while DEET and commercial products containing Icaridin or PMD showed a better response than IR3535 against Ixodes ricinus.

Many plant-based repellents provide only short duration protection. Adding vanillin 5% to plant-based repellents and to DEET repellents increased the protection by about 2 h.

Introduction

Travellers today are confronted with a variety of vector borne threats such as malaria, Dengue, Japanese Encephalitis and tick-borne diseases. These diseases also represent major public health problems for populations living in endemic regions.

The aim of this review is to examine the literature regarding repellent efficacy over the last 12 years (from 2000 to 2012) with the intention of evaluating the efficacy against biting vectors transmitting these diseases and of investigating if one compound is effective against all vectors or if repellents have to be specifically tailored to the profile of vector borne diseases at the destination.

Use of insect repellents is known since antiquity, when burning plant leaves was a common way to keep mosquitoes away from houses, and herbs were handled and applied on the skin as repellent substances [1].

Citronella oil, dimethyl phthalate, Indalone® and Rutgers 612 were common repellent substances before the Second World War [1]. DEET was discovered as a mosquito repellent by the US Department of Agriculture and patented by the US Army in 1946. In 1957, it was allowed for public use and since then it has been a standard repellent [2].

A repellent is defined as a chemical volatile substance that induces arthropods to move in the opposite direction from its source [3]. Ideally, repellents should protect against as many biting insects as possible for a preferably long period of time and cause no adverse reactions [4].

Insect repellents are produced in many different chemical forms such as sprays, creams, lotions, aerosols, oils and grease sticks. The type of formulation plays an important role in the efficacy of a substance [5], [6].

Repellency time depends on several factors and each compound has a different intrinsic protection which varies between mosquito species [7].

Initially, there is typically a period in which the substance repels all mosquitoes and no landing or biting is observed, followed by a period in which the substance loses some of its effect and mosquitoes land on the treated skin. When the effect of the repellent is completely lost, mosquitoes start biting [8].

Human hosts attract mosquitoes also when repellents are applied, however they are repelled in close proximity to the host because of volatile components emanating from the repellent depending on its boiling point, which determines the evaporation from the skin and consequently the distance at which the mosquitoes turn away [7]. Generally this barrier extends for a few centimetres from the skin after immediate application of the repellent, which requires the compound to be uniformly smeared on the exposed skin areas [5], [7].

Air temperature, humidity and wind speed are external factors that influence the efficacy of repellents: in warm, humid climates or at high wind speed the effective duration of the repellent is generally lower and frequent reapplications are needed [7].

Loss of effectiveness is determined by the rate of evaporation of the repellents and by percutaneous penetration. In addition, repellents easily lose their efficacy by being washed off the skin and when rubbed by clothes or objects. Sweating, apart from attracting mosquitoes, dilutes the repellent and reduces the efficacy of the compound [7]. Products containing alcohol are thought to permeate deeper into the skin, which results in a faster loss of effectiveness [6].

Each mosquito species has preferences in biting time, host and habitat [9].

About 950 species have been described around the world. Some species are important vectors of viruses such as Dengue fever and Chikungunya, West Nile Virus and in some areas also filariasis [9].

Dengue fever is an arboviral infection caused by a flavivirus transmitted by Ae. aegypti or Ae. albopictus mosquitoes and occurs in tropical regions, mostly in urban areas [10], and occasionally in Europe [11]. The incidence of the disease has increased over the last decades becoming a major international public health problem. In 2010, over 2.3 million cases have been registered in America, South-east Asia and the Western Pacific and over 40% of the world's population is now at risk [12].

Chikungunya1 is an alphavirus transmitted by Ae. aegypti or Ae. albopictus usually in sub-Saharan Africa, India and Southeast Asia, but recently expanded to Europe [11], [13].

Ae. aegypti's preferred habitat is in proximity to cleaned water reservoirs indoors and outdoors, while Ae. albopictus prefers natural reservoirs in gardens or forests and usually bites outdoors. This mosquito species are day biters and typically bite in crepuscular periods (dawn and dusk) [9].

About 500 species of Anophelines have been described around the world and more than 50 species can transmit malaria through a bite of an infected mosquito female [14], [15].

In 2010, about 3.3 billion people were estimated to be at risk for malaria with people living in sub-Saharan Africa having the highest risk of contracting the disease [15].

It was shown that Plasmodium falciparum sporozoites in An. gambiae can interfere with the mosquitoes' behaviour and induce them to take longer and more frequent blood meals than uninfected mosquitoes, which increases the number of host contacts and the likelihood of disease transmission [16].

In some areas, the genus Anopheles can also transmit Wuchereria bancrofti, the parasite responsible for lymphatic filariasis [9].

Anopheles genus is active during the night and shows species preferences in biting times [9].

Mosquito females feed on both animals and humans and the attractiveness of odours differs between Anopheles species: An. gambiae tends to be highly anthropophilic (preferring humans) and An. quadriannulatus rather zoophilic (preferring animals), whilst An. arabiensis is more opportunistic and can be more attracted to human hosts or animals, depending on region and host availability [17], [18], [19].

About 550 species of Culex mosquitoes have been registered around the world [9].

This mosquito genus is active during the night, both indoors and outdoors [9].

Culex quinquefasciatus, the most common species of this genus, transmits bancroftian filariasis and typically lives in the proximity of polluted water (waste or organic) in developing countries, while Culex tritaeniorhynchus, which transmits Japanese Encephalitis in Asia, prefers cleaner water and lives in ditches or rice fields [9], [20].

Only female mosquitoes bite: male mosquitoes feed primarily on flower nectar, while females require energy from a blood-meal to produce eggs [9].

Periodicity of biting follows an endogenous rhythm but in response to external stimuli, female mosquitoes adapt their behaviour towards sugar feeding or blood-host seeking depending on age, size, nutritional state and gonotrophic stage [14], [21].

In laboratory trials, it was shown that in periods of low energy levels, the attraction to nectar was stronger than to humans in both males and young females. In nature, this attraction depends on the concentration and localization of human and plant odours that interact with host-seeking behaviour [21], [22].

Visual stimuli and human volatile substances are detected by mosquitoes from a distance, while heat, air moisture, movements and use of repellents play a key role in proximity of mosquito hosts for approaching, landing and biting [2], [21], [23].

Mosquito females can visually localize hosts at a distance of more than 50–100 m because of host movements and colours. Thereby they are more attracted to dark colours than light ones [2], [4]. However, it was reported that day-biters supposedly do not see colours but rather contours against light background, and night-biters operate mainly during full moon nights when the lighting allows a better orientation [21].

Olfaction is probably the most important stimulus used by mosquito females to detect (human) blood sources. Mosquito olfactory receptors are located on the antennae and on the maxillae [21].

Carbon dioxide from breathing and human skin emanations is responsible for mosquito olfactory attraction and combined with body temperature may be involved in mosquito biting preferences for different body regions [2]. An. gambiae apparently, is strongly drawn to human sweat and is more likely to bite in the ankle-foot region. Other mosquitoes show preference to biting in the face, which is thought to be due to the expiration of carbon dioxide through the mouth [21].

Different odours play an important role in mosquito attraction: differences in sweat gland outputs and metabolic activity of skin microflora such as Corynebacteria and Malassezia (Pytirosporum) are thought to be responsible for divergent attractiveness to An. gambiae. In the same way, mosquitoes are more attracted to adults and men rather than children or women, and larger persons are prone to mosquito bites because of greater skin emanations and carbon dioxide expiration [2], [21], [24]. Use of fragrances, perfumes, soaps and body lotions may also contribute to attracting mosquitoes [2].

An. stephensi is equally attracted and activated by CO2, which attracts mosquitoes and simultaneously triggers their flight motion. The response to carbon dioxide from human breath in An. gambiae and Cx. quinquefasciatus plays only a secondary role compared to skin released CO2 [21], [23].

Lactic acid is probably the main attractant of Ae. aegypti, and carboxylic acids in human skin secretions also contribute to attracting Ae. aegypti and An. gambiae [21], [23].

An. gambiae and An. stephensi were shown to be strongly activated by acetone, a component of vertebrate breath, while Cx. quinquefasciatus did not present a positive response [23]. Attractiveness in Anophelines to ammoniac, lactic acid, 1-octen-3-ol, oestradiol, cadaverine and lysine has also been demonstrated [4], [21].

Acetone and CO2 activate movements in An. gambiae in the laboratory when presented in concentrations similar to those produced by humans, whilst the same was observed in An. stephensi and An. quadriannulatus when exposed to concentrations typically produced by animals [21].

In contrast to mosquitoes, there are much fewer studies from the time period of our review, conducted on tick behaviour and repellence mechanisms [6].

Ticks detect hosts with sensory receptors located on the front legs and mechanical stimuli provoke them to bite [4], [6].

Olfaction and tactile chemoreception are involved in tick attraction to hosts: carbon dioxide, butyric and  lactic acid as well as heat, shadows and vibrations provoke host seeking behaviour [6].

Section snippets

Search strategies and inclusion criteria

Publications of repellent efficacy written between 2000 and 2012 were the focus of this review.

These publications were searched using PubMed. In the case of papers published by BioOne, only the abstract was available in PubMed and in order to retrieve the full text Google Scholar was used.

The search terms were ‘repellent efficacy’, ‘mosquito repellent’, ‘mosquito repellents’, ‘tick repellent’ and ‘tick repellents’.

We also searched ‘repellent efficacy’ in other languages: Italian, German, French

Results

The search results as of January 1st 2013 for the different terms were: ‘repellent efficacy’ 267 results (216 between 2000 and 2012), ‘mosquito repellent’ 643 results (438 between 2000 and 2012), ‘mosquito repellents’ 886 results (547 between 2000 and 2012), ‘tick repellent’ 132 results (96 between 2000 and 2012) and ‘tick repellents’ 197 results (120 between 2000 and 2012). We reviewed and screened 102 publications that satisfied our selection criteria, namely, they included details of the

Discussion

We summarized our main results in Table 1, but complete details of the studies evaluated can be shown in the long tables subdivided by repellent and mosquito or tick species (Table 2, Table 3, Table 4, Table 5, Table 6, Table 7). The tables on plant-based repellents (except for Citriodora) and vanillin are shown as Supplementary files.

Our approach has some limitations. It is difficult to compare the studies conducted on mosquito and tick repellents due to experimental conditions and factors

Conclusions

Our tables show that the choice of repellents can be tailored, to some extent, according to the profile of biting vectors at the travellers' destination.

According to our analysis, Aedes species demonstrated an aggressive biting behaviour and Ae. Aegypti, in particular, proved to be tolerant to many repellent products. Ae. albopictus was easier to repel than Ae. aegypti.

DEET is the most studied insect repellent and at higher concentrations it presented superior efficacy against Aedes species,

Conflict of interest

The authors declare no conflicts of interest with this review.

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