Effectiveness of plant-based repellents against different Anopheles species: a systematic review.

Plant-based repellents have been applied for generations in traditional practice as a personal protection approach against different species of Anopheles. Knowledge of traditional repellent plants is a significant resource for the development of new natural products as an alternative to chemical repellents. Many studies have reported evidence of repellant activities of plant extracts or essential oils against malaria vectors worldwide. This systematic review aimed to assess the effectiveness of plant-based repellents against Anopheles mosquitoes. All eligible studies on the repellency effects of plants against Anopheles mosquitoes published up to July 2018 were systematically searched through PubMed/Medline, Scopus and Google scholar databases. Outcomes measures were percentage repellency and protection time. A total of 62 trials met the inclusion criteria. The highest repellency effect was identified from Ligusticum sinense extract, followed by citronella, pine, Dalbergia sissoo, peppermint and Rhizophora mucronata oils with complete protection time ranging from 9.1 to 11.5 h. Furthermore, essential oils from plants such as lavender, camphor, catnip, geranium, jasmine, broad-leaved eucalyptus, lemongrass, lemon-scented eucalyptus, amyris, narrow-leaved eucalyptus, carotin, cedarwood, chamomile, cinnamon oil, juniper, cajeput, soya bean, rosemary, niaouli, olive, tagetes, violet, sandalwood, litsea, galbanum, and Curcuma longa also showed good repellency with 8 h complete repellency against different species of Anopheles. Essential oils and extracts of some plants could be formulated for the development of eco-friendly repellents against Anopheles species. Plant oils may serve as suitable alternatives to synthetic repellents in the future as they are relatively safe, inexpensive, and are readily available in many parts of the world.

Background

Mosquito-transmitted diseases remain a main source of illness and death [1]. Despite decades of malaria control efforts, malaria continues to be a major worldwide public health issue with 3.3 billion persons at risk in 106 countries and territories in the tropical and subtropical areas [2]. It is one of the significant reasons for maternal and childhood morbidity and mortality, including low birth weight, stillbirths, and early infant death in sub-Saharan Africa [3]. Among 500 species of Anopheles mosquitoes known globally, more than 50 species can transmit malaria from the bite of the infected female Anopheles spp. [4]. Presently, there is no effective prophylactic anti-malarial vaccine and no suitable preventive measure other than vector control is available [5]. Thus, protection from mosquito bites is one of the best approaches to reduce the disease incidence.

The use of repellents to protect people from bites of mosquitoes previously has been acknowledged as part of an overall integrated insect-borne disease control programme [6]. Most commercial repellents are produced by using chemical components such as N, N-diethyl-meta-toluamide (DEET), Allethrin, N, N-diethyl mendelic acid amide, and Dimethyl phthalate [1]. It has been identified that chemical repellents are not safe for public health and should be used with caution because of their detrimental impacts on synthetic fabric and plastic as well as toxic reactions, such as allergy, dermatitis, and cardiovascular and neurological side effects, which have been reported generally after misapplication [4]. The frequent use of synthetic repellents with chemical origin for mosquito control has disturbed natural ecosystems and resulted in the development of resistance to insecticides, resurgence in mosquito populations, and adverse impact on non-target organisms [4, 7]. Accordingly, the idea of using natural mosquito repellent products as an alternative to develop new eco-friendly repellents could be an amicable solution to scale back the undesirable effects on environment and human health.

In recent years, interest in plant-based repellents has been revived, as they contain a rich source of bioactive phytochemicals that are safe and biodegradable into non-toxic by-products, which could be screened for insecticidal activities and mosquito repellent. Many studies have reported evidence of repellant activities of plant extracts or essential oils against malaria vectors around the world. The present systematic review was performed to reveal which plant-based repellent can be relied on to provide a prolonged and predictable protection from species of Anopheles mosquitoes without causing side effects on human health.

For this systematic review, all eligible studies on the repellency effects of plant-based repellants against Anopheles spp. published up to July 2018 were systematically searched through electronic databases PubMed, MEDLINE, Web of Science, Literature retrieval System of the Armed Forces Pest Management Board, Scopus and Google Scholar using the following Medical Subject Headings (Mesh) and keywords: (((Plant [Title/Abstract]) OR Plants [Title/Abstract]) OR herbal [Title/Abstract]) AND (botanical [Title/Abstract]) AND ((extract [Title/Abstract]) OR extracts [Title/Abstract]) AND ((“essential oil” [Title/Abstract]) OR “essential oils” [Title/Abstract]) AND (((((“Insect repellent” [Mesh]) OR repellents) OR repellent) OR repellence) OR repellency) AND ((“Anopheles” [Mesh]) OR “Anopheles” [Title/Abstract]). The search was limited to English publications. In addition, a manual search was conducted to identify further pertinent articles using references from retrieved studies.

Eligibility criteria

Studies were included in the present systematic review if they met these criteria: (i) full-text publication was written in English, (ii) inspected the repellency effects of plant extracts and essential oils against malaria vectors, Anopheles spp. mosquitoes, and, (iii) reported the percentage of repellency or complete protection time. Following studies were excluded: studies exploring the repellency effect of chemical-based products, studies examining the repellency effect of animal extracts, animal studies (studies not on human subjects), articles without full texts, reviews, duplicate articles, abstracts, republished data, comments, conference papers, editorials, and studies with insufficient data. In addition, studies were excluded if the information could not be extracted. A screening of titles and abstracts followed by a full-text review was performed by two investigators. All titles and abstracts were screened by two independent investigators for eligibility. If a consensus was reached, a study was excluded or selected to full-text screening. If a consensus was not reached, another reviewer was consulted to resolve any feasible discrepancies.

Data extraction

After identifying the eligible studies, the following data were collected from each study by application of standardized data collection form to improve accuracy and critical appraisal: the first author name, country of origin, journal details, publication year, condition of study (field or laboratory), plant name, Anopheles species, concentration or dose of repellents, repellency percentage and complete protection time. All data were independently extracted by two reviewers and disagreements were solved by discussion, and if necessary, a third author was involved.

A total of 383 studies were found by the initial literature search of the databases. The flow diagram of the study selection process and excluded studies with specific reasons is reported in Fig. 1. Of the 324 excluded citations, 102 were duplicated studies; 149 were not relevant to the repellency effect of plants on Anopheles spp. after screening titles/abstracts; 11 were review publications; 8 investigated the repellency impact of chemical-based repellents or animal extracts; 7 studies were conducted on laboratory animals; 12 were abstracts, conference papers, comments, and editorials; 10 studies had not reported sufficient data regarding the percentage of repellency or complete protection time; and, 15 studies were other irrelevant studies. The primary eligibility process yielded 59 documents and crosscheck of the references of reviews and other databases search provided 3 further articles [8-10]. A total of 62 studies conducted in different countries, including India [7-40], Thailand [4, 5, 41–48], Ethiopia [49-52], Kenya [53-57], Germany [6], Nigeria [1], USA [58], Tanzania [59], Brazil [60], Sudan [61], Iran [62], Cameron [63] and Ivory Coast [64] were eventually included in the systematic review based on the inclusion criteria for the effect of plant-based repellents on species of Anopheles mosquitoes. The included studies were published between 1999 and 2018. Expect for 6 studies which were field trial, other studies were conducted on laboratory condition. None of the studies reported the inclusion and exclusion criteria explicitly other than specifying a healthy volunteer. Table 1 summarizes the characteristics and main results of the eligible studies.

Fig. 1

Study selection process, up to July 2018

Table 1

Characteristics of studies. Characteristics of studies included in the systematic review, up to July 2018

Study	Year	Country	Study type	Plant extract/(essential oil)	Concentration dose	Anopheles species	Repellency %	Protection time (hours)
Ansari et al.	2005	India	Field	Pine oil (Pinus)	1 ml without dilution	An. culicifacies	100	11
				Citronella (lemongrass oil)	1 ml without dilution	An. culicifacies	100	11
Ansari et al.	2000	India	Field	D. sissoo oil	1 ml without dilution	An. culicifacies	96.1	10.3
				D. sissoo oil	1 ml without dilution	An. annularis	100	11
				D. sissoo oil	1 ml without dilution	An. subpictus	89.7	8
Ansari et al.	2000	India	Field	Peppermint oil	1 ml without dilution	An. culicifacies	92.3	9.6
				Peppermint oil	1 ml without dilution	An. annularis	100	11
				Peppermint oil	1 ml without dilution	An. subpictus	83.1	7.3
Amer et al.	2006	Germany	Laboratory	Citronella (Cymbopogon winterianus) essential oils	20% oil solutions	An. stephensi	52.4	8
				Rosewood (Aniba rosaeodora) essential oils	20% oil solutions	An. stephensi	4.8	6.5
				Lavender (Lavandula angustifolia) essential oils	20% oil solutions	An. stephensi	80.9	8
				Camphor (C. camphora) essential oils	20% oil solutions	An. stephensi	42.8	8
				Catnip (N. cataria) essential oils	20% oil solutions	An. stephensi	100	8
				Geranium (Pelargonium graveolens) essential oils	20% oil solutions	An. stephensi	61.9	8
				Thyme (T. serpyllum) essential oils	20% oil solutions	An. stephensi	33.3	7.5
				Eucalyptus (E. globulus) essential oils	20% oil solutions	An. stephensi	28.6	5.5
				Jasmine (Jasminum grandiflorum) essential oils	20% oil solutions	An. stephensi	100	8
				Broad-leaved eucalyptus (Eucalyptus dives) essential oils	20% oil solutions	An. stephensi	38.1	8
				Lemongrass (Cymbopogon citratus) essential oil	20% oil solutions	An. stephensi	100	8
				Lemon-scented eucalyptus (E. citriodora) essential oil	20% oil solutions	An. stephensi	52.4	8
				Fichtennadel (Picea excelsa) essential oil	20% oil solutions	An. stephensi	19	3
				Amyris (Amyris balsamifera) essential oil	20% oil solutions	An. stephensi	100	8
				Lemon (Citrus limon) essential oil	20% oil solutions	An. stephensi	9.5	7
				Narrow-leaved eucalyptus (Eucalyptus radiata) essential oil	20% oil solutions	An. stephensi	42.8	8
				Carotin oil (Glycina soja) essential oil	20% oil solutions	An. stephensi	9.5	8
				Cedarwood (Juniperus virginiana) essential oil	20% oil solutions	An. stephensi	38.1	8
				frankincense (Boswellia carteri) essential oil	20% oil solutions	An. stephensi	19	5
				Dill (Anethum graveolens) essential oil	20% oil solutions	An. stephensi	71.4	3.5
				Myrtle (M. communis) essential oil	20% oil solutions	An. stephensi	42.8	6.5
				Chamomile (Anthemis nobilis) essential oil	20% oil solutions	An. stephensi	76.2	8
				Cinnamon (C. zeylanicum) essential oil	20% oil solutions	An. stephensi	100	8
				Juniper (Juniperus communis) essential oil	20% oil solutions	An. stephensi	76.2	8
				Sage (Salvia sclarea) essential oil	20% oil solutions	An. stephensi	19	5
				Peppermint (Mentha piperita) essential oil	20% oil solutions	An. stephensi	57.1	6.5
				Basil (Ocimum basilicum) essential oil	20% oil solutions	An. stephensi	66.7	3.5
				Cajeput (Melaleuca leucadendron) essential oil	20% oil solutions	An. stephensi	100	8
				Soya bean (Glycina max) essential oil	20% oil solutions	An. stephensi	76.2	8
				Rosemary (R. officinalis) essential oil	20% oil solutions	An. stephensi	100	8
				Niaouli (Melaleuca quinquenervia) essential oil	20% oil solutions	An. stephensi	100	8
				Olive (O. europaea) essential oil	20% oil solutions	An. stephensi	71.4	8
				Black pepper (Piper nigrum) essential oil	20% oil solutions	An. stephensi	61.9	3
				Verbena (Lippia citriodora) essential oil	20% oil solutions	An. stephensi	38.1	5.5
				tagetes (T. minuta) essential oil	20% oil solutions	An. stephensi	100	8
				Violet (Viola odorata) essential oil	20% oil solutions	An. stephensi	100	8
				Sandalwood (Santalum album) essential oil	20% oil solutions	An. stephensi	100	8
				Litsea (Litsea cubeba) Essential oil	20% oil solutions	An. stephensi	100	8
				Helichrysum (Helichrysum italicum) essential oil	20% oil solutions	An. stephensi	47.6	6
				Galbanum (Ferula galbaniflua) essential oil	20% oil solutions	An. stephensi	100	8
				Chamomile (Chamaemelum nobile) essential oil	20% oil solutions	An. stephensi	47.6	5.5
Amerasan et al.	2012	India	Laboratory	Cassia tora Linn methanol extract	1 mg/cm2 2.5 mg/cm2 5.0 mg/cm2	An. stephensi	100 100 100	2 2 2.5
Abiy et al.	2015	Ethiopia	Field	20% neem oil	Neem and chinaberry oils were diluted to 20% using Niger seed (noog abyssinia) oil	An. arabiensis	71	3
				20% chinaberry oil	Neem and chinaberry oils were diluted to 20% using Niger seed (noog abyssinia) oil	An. arabiensis	70	1
Alayo et al.	2015	Nigeria	Laboratory	Cassia mimosoides petroleum ether extract	Cream 0.5% w/w	An. gambiae	48	–
					Cream 1% w/w		88	–
					Cream 2% w/w		100	0.08
					Cream 4% w/w		100	0.08
					Cream 6% w/w		100	0.08
Alwala et al.	2010	Kenya	Laboratory	Mangifera indica essential Oil	10% solution	An. gambiae	100	–
Baskar et al.	2018	India	Laboratory	Atalantia monophylla essential oil	50 ppm	An. stephensi	–	6.85
Govindarajan et al.	2010	India	Laboratory	Sida acuta Burm. F. extract	2.5 mg/cm2	An. stephensi	100	2.5
					5 mg/cm2	An. stephensi	100	3
Govindarajan et al.	2011	India	Laboratory	Ervatamia coronaria extract	1 mg/cm2 2.5 mg/cm2 5 mg/cm2	An. stephensi An. stephensi An. stephensi	100 100 100	2.5 3 3.5
				Caesalpinia pulcherrima extract	1 mg/cm2	An. stephensi	100	2
					2.5 mg/cm2	An. stephensi	100	2.5
Govindarajan et al.	2011	India	Laboratory		5 mg/cm2	An. stephensi	100	3
					2.5 mg/cm2 5 mg/cm2	An. subpictus An. subpictus	100 100	2 2.5
				R. officinalis L. essential oil	1 mg/cm2	An. subpictus	100	1
					2.5 mg/cm2	An. subpictus	100	1
					5 mg/cm2	An. subpictus	100	1.5
				C. citrates Stapf. essential oil	1 mg/cm2	An. subpictus	100	1
					2.5 mg/cm2	An. subpictus	100	1.5
					5 mg/cm2	An. subpictus	100	2
				C. zeylanicum L. essential oil	1 mg/cm2	An. subpictus	100	1
					2.5 mg/cm2	An. subpictus	100	1
					5 mg/cm2	An. subpictus	100	1.5
Govindarajan et al.	2016	India	Laboratory	Zingiber nimmonii essential oil	1 mg/cm2	An. stephensi	100	2
					2 mg/cm2	An. stephensi	100	2.5
					5 mg/cm2	An. stephensi	100	3
Jeyabalan et al.	2003	India	Laboratory	P. citrosa leaf extract	0.5%	An. stephensi	36	–
					1%	An. stephensi	51	–
					2%	An. stephensi	78	–
					4%	An. stephensi	100	–
Karunamoorthi et al.	2008	Ethiopia	Laboratory	Woira (O. europaea) smoke	Burning of 25 g of dried plant materials	An. arabiensis	79.7	–
				Tinjut (Ostostegia integrifolia) smoke	Burning of 25 g of dried plant materials	An. arabiensis	90.1	–
				Wogert (Silene macroserene) smoke	Burning of 25 g of dried plant materials	An. arabiensis	93.6	–
				Kebercho (Echinops sp.) extract	Burning of 25 g of dried plant materials	An. arabiensis	92.4	–
Karunamoorthi et al.	2010	Ethiopia	Laboratory	C. citratus extract	1 mg/cm2	An. arabiensis	100	3.2
					1.5 mg/cm2	An. arabiensis	100	4.4
					2 mg/cm2	An. arabiensis	100	5.3
					2.5 mg/cm2	An. arabiensis	100	6.3
Govindarajan et al.	2016	India	Laboratory	Origanum scabrum essential oil	1 mg/cm2	An. stephensi	100	2.5
					2 mg/cm2	An. stephensi	100	3
					5 mg/cm2	An. stephensi	100	3.5
Haldar et al.	2014	India	Laboratory	Ficus krishnae smoke	30 mg/l smoked	An. stephensi	18	0.16
					60 mg/l smoked	An. stephensi	100	0.5
					90 mg/l smoked	An. stephensi	100	1
Auysawasdi et al.	2015	Thailand	Laboratory	Curcuma longa essential oil	5%	An. dirus	100	4
					10%	An. dirus	100	5
					15%	An. dirus	100	5.5
					20%	An. dirus	100	5.5
					25%	An. dirus	100	8
				E. globulus essential oil	5%	An. dirus	100	1.7
					10%	An. dirus	100	2.3
					15%	An. dirus	100	3
					20%	An. dirus	100	3
					25%	An. dirus	100	3.4
				Citrus aurantium essential oil	5%	An. dirus	100	1.8
					10%	An. dirus	100	2.9
					15%	An. dirus	100	2.9
					20%	An. dirus	100	3
					25%	An. dirus	100	3.5
Barnard et al.	1999	USA	Laboratory	Clove essential oil	25%	An. albimanus	100	1.25
					50%	An. albimanus	100	1.5
					75%	An. albimanus	100	2.26
					100%	An. albimanus	100	3.55
				Thyme essential oil	25%	An. albimanus	100	0.75
					50%	An. albimanus	100	0.5
					75%	An. albimanus	100	1
					100%	An. albimanus	100	1.75
Kweka et al.	2008	Tanzania	Laboratory	Citronella	500 mg/m2	An. gambiae	81	–
				Ocimum suave extract	500 mg/m2	An. gambiae	81	–
				Ocimum kilimandscharicum extract	500 mg/m2	An. gambiae	73	–
				Citronella	500 mg/m2	An. arabiensis	85	–
				O. suave extract	500 mg/m2	An. arabiensis	89	–
				O. kilimandscharicum extract	500 mg/m2	An. arabiensis	75	–
Kovendan et al.	2012	India	Laboratory	A. alnifolia extract	1 mg/cm2	An. stephensi	100	2
					3 mg/cm2	An. stephensi	100	2
					5 mg/cm2	An. stephensi	100	2.5
Krishnappa et al.	2012	India	Laboratory	A. digitata crude extract	2 mg/cm2	An. stephensi	100	3
					4 mg/cm2	An. stephensi	100	3.5
					6 mg/cm2	An. stephensi	100	3.5
Naine et al.	2014	India	Laboratory	Streptomyces sp. VITJS4 extract	1 mg/cm2	An. stephensi	100	2
					3 mg/cm2	An. stephensi	100	2
					6 mg/cm2	An. stephensi	100	2
Murugan et al.	2012	India	Laboratory	Orange peel extract	50 ppm	An. stephensi	99	–
					150 ppm	An. stephensi	100	0.5
					250 ppm	An. stephensi	100	0.05
					350 ppm	An. stephensi	100	1.5
					450 ppm	An. stephensi	100	2
Padilha et al.	2003	Brazil	Field	Ocimum selloi oil	10% v/v	An. braziliensis	89	0.5
Konan et al.	2003	Ivory Coast	Laboratory	Karite nut butter oil	75%	An. gambiae	100	2
				Palm oil	75%	An. gambiae	100	1.38
				Coconut oil	75%	An. gambiae	100	0.76
Maheswaran et al.	2013	India	Laboratory	Confertifolin essential oil	0.62 ppm	An. stephensi	100	1
					1.25 ppm	An. stephensi	100	2.5
					2.5 ppm	An. stephensi	100	3
					5 ppm	An. stephensi	100	5
					10 ppm	An. stephensi	100	5.2
Panneerselvam et al.	2013	India	Laboratory	Andrographis paniculata methanol leaf extract	1 mg/cm2	An. stephensi	100	2
					3 mg/cm2	An. stephensi	100	2.5
					6 mg/cm2	An. stephensi	100	3
				Cassia occidentalis methanol leaf extract	1 mg/cm2	An. stephensi	100	2
					3 mg/cm2	An. stephensi	100	2.5
					6 mg/cm2	An. stephensi	100	2.5
				Euphorbia hirta methanol leaf extract	1 mg/cm2	An. stephensi	100	2
					3 mg/cm2	An. stephensi	100	2
					6 mg/cm2	An. stephensi	100	2.5
Panneerselvam et al.	2012	India	Laboratory	Artemisia nilagirica extract	50 ppm	An. stephensi	95	0.5
					150 ppm	An. stephensi	98	0.5
					250 ppm	An. stephensi	100	0.5
					350 ppm	An. stephensi	100	1
					450 ppm	An. stephensi	100	2
Phasomkusolsil et al.	2011	Thailand	Laboratory	Cananga odorata oil	0.02 mg/cm2	An. dirus	94	–
					0.10 mg/cm2	An. dirus	92	–
					0.21 mg/cm2	An. dirus	92	–
				C. sinensis oil	0.02 mg/cm2	An. dirus	40	–
					0.10 mg/cm2	An. dirus	54	–
					0.21 mg/cm2	An. dirus	84	–
				C. citratus oil	0.02 mg/cm2	An. dirus	76	–
					0.10 mg/cm2	An. dirus	82	–
					0.21 mg/cm2	An. dirus	98	–
				Cymbopogon nardus oil	0.02 mg/cm2	An. dirus	92	–
					0.10 mg/cm2	An. dirus	92	–
					0.21 mg/cm2	An. dirus	98	–
				E. citriodora oil	0.02 mg/cm2	An. dirus	52	–
					0.10 mg/cm2	An. dirus	74	–
					0.21 mg/cm2	An. dirus	86	–
				O. basilicum oil	0.02 mg/cm2	An. dirus	66	–
					0.10 mg/cm2	An. dirus	74	–
					0.21 mg/cm2	An. dirus	96	–
				S. aromaticum oil	0.02 mg/cm2	An. dirus	82	–
					0.10 mg/cm2	An. dirus	92	–
					0.21 mg/cm2	An. dirus	98	–
Prabhu et al.	2011	India	Laboratory	Moringa oleifera extract	20%	An. stephensi	23	–
					40%	An. stephensi	43	–
					60%	An. stephensi	58	–
					80%	An. stephensi	76	–
					100%	An. stephensi	90	–
Rajkumar et al.	2007	India	Laboratory	Centella asiatica essential oil	2%	An. stephensi	–	1
					4%	An. stephensi	–	1.78
					6%	An. stephensi	–	2.33
				Ipomoea cairica essential oil	2%	An. stephensi	–	2.63
					4%	An. stephensi	–	4.13
					6%	An. stephensi	–	5.53
				Momordica charantia essential oil	2%	An. stephensi	–	2.38
					4%	An. stephensi	–	3.93
					6%	An. stephensi	–	5.38
				Psidium guajava essential oil	2%	An. stephensi	–	0.93
					4%	An. stephensi	–	1.48
					6%	An. stephensi	–	1.98
				Tridax procumbens essential oil	2%	An. stephensi	–	2.33
					4%	An. stephensi	–	3.78
					6%	An. stephensi	–	5.28
Rajkumar et al.	2005	India	Laboratory	Solanum trilobatum extract	0.001%	An. stephensi	100	1.15
					0.005%	An. stephensi	100	1.3
					0.01%	An. stephensi	100	1.51
					0.015%	An. stephensi	100	1.7
					0.02%	An. stephensi	100	2.03
Rawani et al.	2012	India	Laboratory	P. tuberosa extract	1%	An. stephensi	65	2.3
					1.50%	An. stephensi	80	4
					2%	An. stephensi	90	5
Reegan et al.	2015	India	Laboratory	Cliona celata extract	1 mg/cm2	An. stephensi	100	1.08
					2.5 mg/cm2	An. stephensi	100	1.71
					5 mg/cm2	An. stephensi	100	1.21
Swathi et al.	2012	India	Laboratory	Datura stramonium extract	0.1%	An. stephensi	–	0.35
					0.5%	An. stephensi	–	0.72
					1%	An. stephensi	–	1.9
Seyoum et al.	2002	Kenya	Semi-field	Neem (A. indica)	Periodic thermal expulsion	An. gambiae	24.5	–
				Lemon eucalyptus (Corymbia citriodora)	Periodic thermal expulsion	An. gambiae	74.5	–
				Wild spikenard (Hyptis suaveolens)	Periodic thermal expulsion	An. gambiae	-13.3	–
				Lantana (Lantana camara)	Periodic thermal expulsion	An. gambiae	42.4	–
				Fever tea (Lippia uckambensis)	Periodic thermal expulsion	An. gambiae	45.9	–
				Lime basil (Ocimum americanum)	Periodic thermal expulsion	An. gambiae	43.1	–
				Rican blue basil (O. kilimandscharicum)	Periodic thermal expulsion	An. gambiae	52.0	–
				Tree basil (O. suave)	Periodic thermal expulsion	An. gambiae	53.1	–
				Khaki weed (T. minuta)	Placing branches or whole plants inside houses	An. gambiae	54.8	–
Sanghong et al.	2015	Thailand	Laboratory	L. sinense ethanolic preparations	25%	An. minimus	–	11.5
Das et al.	2003	India	Laboratory	Cymbopogan martinii martinii var sofia oil	1 ml without dilution	An. sundaicus	98	6
Nour et al.	2009	Sudan	Laboratory	Basil (O. basilicum L.) essential oil	0.1 ml		100	1.5
Trongtokit et al.	2005	Thailand	Laboratory	C. nardus essential oil	10%	An. dirus	–	0.66
					50%		–	0.5
					100%		–	1.16
				P. cablin essential oil	10%	An. dirus	–	1.33
					50%		–	2
					100%		–	2.83
				Mullilam (Zanthoxylum limonella) essential oil	10%	An. dirus	–	1
					50%		–	2.16
					100%		–	3.16
				Clove (Syzygium aromaticum) essential oil	10%	An. dirus	–	1.33
					50%		–	2.66
					100%		–	3.5
Yogananth et al.	2015	India	Laboratory	R. mucronata oil	1 mg/cm2	An. stephensi	73	7.2
					2 mg/cm2	An. stephensi	86	7.8
					3 mg/cm2	An. stephensi	92	8.5
					4 mg/cm2	An. stephensi	97	9.1
Tawatsin et al.	2000	Thailand	Laboratory	Turmeric (C. longa) volatile oil	3 ml	An. dirus	100	6
				Citronella	3 ml	An. dirus	100	6
				Hairy basil oil	3 ml	An. dirus	100	6
Singh et al.	2005	India	Laboratory	Cyperus rotundus Linn hexane extract	2.50%	An. stephensi	95	–
					5%	An. stephensi	99	–
					10%	An. stephensi	100	6
Mayeku et al.	2013	Kenya	laboratory	Conyza newii essential oil	0.01 g/ml	An. gambiae	38	–
					0.1 g/ml	An. gambiae	68	–
					1 g/ml	An. gambiae	100	–
Phasomkusolsil et al.	2009	Thailand	Laboratory	Phlai (Z. cassumunar) oil	100 μl	An. minimus	–	2
				Turmeric (C. longa) oil	100 μl	An. minimus	–	1
				Mah-Khwuaen (Z. limonella) oil	100 μl	An. minimus	–	0.66
				Citronella grass (C. nardus) oil	100 μl	An. minimus	–	2.16
				Orange oil (Citrus sinensis) oil	100 μl	An. minimus	–	0.83
				Eucalyptus (E. citriodora) oil	100 μl	An. minimus	–	0.5
				Clove (S. aromaticum) oil	100 μl	An. minimus	–	2
Trongtokit et al.	2004	Thailand	Laboratory	Clove oil	20% gel	An. dirus	–	4.5
					cream 20%	An. dirus	–	4.8
Birkett et al.	2011	Kenya	Laboratory	N. cataria	0.01 mg	An. gambiae	17	–
					0.1 mg	An. gambiae	97	–
					1 mg	An. gambiae	100	–
Kamaraj et al.	2011	India	Laboratory	A. concinna extract	500 ppm	An. stephensi	21	–
Solomon et al.	2012	Ethiopia	Laboratory	Citronella extract	20%	An. Arabiensis	73	–
Soonwera et al.	2015	Thailand	Laboratory	C. odorata oil	1%	An. dirus	92	–
					5%	An. dirus	92	–
					10%	An. dirus	94	–
Sritabutra et al.	2011	Thailand	Laboratory	Eucalyptus (E. globules) essencial oil	0.1 ml	An. dirus	–	1.58
				Peppermint (M. piperita) essencial oil	0.1 ml	An. dirus	–	1.08
				Garlic (A. sativum) essencial oil	0.1 ml	An. dirus	–	0.68
				Orange (C. sinensis) essencial oil	0.1 ml	An. dirus	–	0.83
				Citronella grass (C. nardus) essencial oil	0.1 ml	An. dirus	–	0.8
				Lemongrass (C. citratus) essencial oil	0.1 ml	An. dirus	–	1.63
				Clove (S. aromaticum) essencial oil	0.1 ml	An. dirus	–	1
				Sweet basil (O. basilicum) essencial oil	0.1 ml	An. dirus	–	0.75
Tavassoli et al.	2001	iran	Laboratory	Marigold (Calendula officinalis) essential oil	50%	An. stephensi	–	2.15
				Myrtle essential oil	50%	An. stephensi	–	4.36
Younoussa et al.	2016	Cameroon	Laboratory	Annona senegalensis leaf extract	4.0 mg/cm2	An. gambiae	–	0.5
					8.0 mg/cm2	An. gambiae	–	1
					12.0 mg/cm2	An. gambiae	–	1.5
				Boswellia dalzielii leaf extract	4.0 mg/cm2	An. gambiae	46
					8.0 mg/cm2	An. gambiae	–	0.5
					12.0 mg/cm2	An. gambiae	–	1
Govindarajan et al.	2011	India	Laboratory	Coccinia indica extract	1 mg/cm2	An. stephensi	100	3
					2.5 mg/cm2	An. stephensi	100	3
					5 mg/cm2	An. stephensi	100	3.5
Govindarajan et al.	2012	India	Laboratory	Cardiospermum halicacabum oil	1 mg/cm2	An. stephensi	100	2
					2.5 mg/cm2	An. stephensi	100	2.5
					5 mg/cm2	An. stephensi	100	3
Govindarajan et al.	2014	India	Laboratory	Asparagus racemosus crude extract	1 mg/cm2	An. stephensi	100	2.5
					2 mg/cm2	An. stephensi	100	2.5
					5 mg/cm2	An. stephensi	100	3
Govindarajan et al.	2015	India	Laboratory	Delonix elata crude extract	1 mg/cm2	An. stephensi	100	2.5
					2.5 mg/cm2	An. stephensi	100	3
					5 mg/cm2	An. stephensi	100	3.5
Innocent et al.	2014	Kenya	Laboratory	Uvariodendron gorgonis essential oil	0.01 w/v	An. gambiae	29	–
					0.1 w/v	An. gambiae	48	–
					1 w/v	An. gambiae	57	–
					10 w/v	An. gambiae	64	–
				Clausena anisata essential oil	0.01 w/v	An. gambiae	13	–
					0.1 w/v	An. gambiae	21	–
					1 w/v	An. gambiae	42	–
					10 w/v	An. gambiae	56	–
				Lantana vibunoides essential oil	0.01 w/v	An. gambiae	26	–
					0.1 w/v	An. gambiae	46	–
					1 w/v	An. gambiae	54	–
					10 w/v	An. gambiae	62	–
Kumar et al.	2012	India	Laboratory	Sargassum wightii Greville methanolic extract	2 mg/l	An. sundaicus	26	–
					4 mg/l	An. sundaicus	40	–
					6 mg/l	An. sundaicus	57	–
					8 mg/l	An. sundaicus	71	–
					10 mg/l	An. sundaicus	89	–
Madhiyazhagan et al.	2014	India	Laboratory	O. canum extract	0.49 mg/l	An. stephensi	63	–
					0.99 mg/l	An. stephensi	77	–
					1.99 mg/l	An. stephensi	86	–

Effectiveness of plant-based products against Anopheles spp.

Potential plant-based repellents stratified by protection time with at least 4 h protection time are reported in Table 2. The highest repellency effect was identified from Ligusticum sinense extract, followed by citronella, pine, Dalbergia sissoo, peppermint and Rhizophora mucronata oils with complete protection time ranging from 9.1 to 11.5 h. Ethanolic 25% extract of L. sinense was able to completely repel Anopheles minimus for 11.5 h. Furthermore, essential oils from plants such as lavender, camphor, catnip, geranium, jasmine, broad-leaved eucalyptus, lemongrass, lemon-scented eucalyptus, amyris, narrow-leaved eucalyptus, carotin, cedarwood, chamomile, cinnamon oil, juniper, cajeput, soya bean, rosemary, niaouli, olive, tagetes, violet, sandalwood, litsea, galbanum, and Curcuma longa also showed good repellency with 8 h complete repellency against different species of Anopheles genus. Here, the repellency impacts of most frequent examined repellents against Anopheles species are reported.

Table 2

Stratification of potential of plant based repellents

Protection time (hours)	Plant name	Concentration/dose	Anopheles species
11.5	L. sinense ethanolic extract	25%	An. minimus
11	Pine oil (Pinus) Citronella (lemongrass oil) D. sissoo oil Peppermint oil	1 ml without dilution 1 ml without dilution 1 ml without dilution 1 ml without dilution	An. culicifacies An. culicifacies An. annularis An. annularis
8 < to < 10	D. sissoo oil Peppermint oil R. mucronata oil R. mucronata oil	1 ml without dilution 1 ml without dilution 4 mg/cm2 3 mg/cm2	An. culicifacies An. culicifacies An. stephensi An. stephensi
8	D. sissoo oil	1 ml without dilution	An. subpictus
	Citronella (C. winterianus) essential oils	20% oil solution	An. stephensi
	Lavender (L. angustifolia) essential oils	20% oil solution	An. stephensi
	Camphor (C. camphora) essential oils	20% oil solution	An. stephensi
	Catnip (N. cataria) essential oils	20% oil solution	An. stephensi
	Geranium (P. graveolens) essential oils	20% oil solution	An. stephensi
	Jasmine (J. grandiflorum) essential oils	20% oil solution	An. stephensi
	Broad-leaved eucalyptus (E. dives) essential oils	20% oil solution	An. stephensi
	Lemongrass (C. citratus) essential oil	20% oil solution	An. stephensi
	Lemon-scented eucalyptus (E. citriodora)	20% oil solution	An. stephensi
	Amyris (A. balsamifera) essential oil	20% oil solution	An. stephensi
	Narrow-leaved eucalyptus (E. radiata) essential oil	20% oil solution	An. stephensi
	Carotin oil (G. soja) essential oil	20% oil solution	An. stephensi
	Cedarwood (J. virginiana) essential oil	20% oil solution	An. stephensi
	Chamomile (A. nobilis) essential oil	20% oil solution	An. stephensi
	Cinnamon (C. zeylanicum) essential oil	20% oil solution	An. stephensi
	Juniper (J. communis) essential oil	20% oil solution	An. stephensi
	Cajeput (M. leucadendron) essential oil	20% oil solution	An. stephensi
	Soya bean (G. max) essential oil	20% oil solution	An. stephensi
	Rosemary (R. officinalis) essential oil	20% oil solution	An. stephensi
	Niaouli (M. quinquenervia) essential oil	20% oil solution	An. stephensi
	Olive (O. europaea) essential oil	20% oil solution	An. stephensi
	Tagetes (T. minuta) essential oil	20% oil solution	An. stephensi
	Violet (V. odorata) essential oil	20% oil solution	An. stephensi
	Sandalwood (S. album) essential oil	20% oil solution	An. stephensi
	Litsea (L. cubeba) essential oil	20% oil solution	An. stephensi
	Galbanum (F. galbaniflua) essential oil	20% oil solution	An. stephensi
	C. longa essential oil	25%	An. dirus
7 < to < 8	R. mucronata oil	2 mg/cm2	An. stephensi
	Thyme (T. serpyllum) essential oils	20% oil solutions	An. stephensi
	Peppermint oil	1 ml without dilution	An. subpictus
	R. mucronata oil	1 mg/cm2	An. stephensi
7	Lemon (C. limon) essential oil	20% oil solution	An. stephensi
6 < to < 7	A. monophylla essential oil	50 ppm	An. stephensi
	rosewood (A. rosaeodora) essential oils	20% oil solution	An. stephensi
	myrtle (M. communis) essential oil	20% oil solution	An. stephensi
	peppermint (M. piperita) essential oil	20% oil solution	An. stephensi
6	Helichrysum (H. italicum) essential oil	20% oil solution	An. stephensi
	C. martinii martinii var sofia oil	1 ml without dilution	An. sundaicus
	Turmeric (C. longa) volatile oil	3 ml	An. dirus
	Citronella	3 ml	An. dirus
	Hairy basil oil	3 ml	An. dirus
	C. rotundus Linn hexane extract	10%	An. stephensi
5 < to < 6	I. cairica essential oil	6%	An. stephensi
	Eucalyptus (E. globulus) essential oils	20% oil solution	An. stephensi
	Verbena (L. citriodora) essential oil	20% oil solution	An. stephensi
	Chamomile (C. nobile) essential oil	20% oil solution	An. stephensi
	C. longa essential oil	15%	An. dirus
	C. longa essential oil	20%	An. dirus
	M. charantia essential oil	6%	An. stephensi
	C. citratus extract	2 mg/cm2	An. arabiensis
	T. procumbens essential oil	6%	An. stephensI
	Confertifolin essential oil	10 ppm	An. stephensi
5	Frankincense (B. carteri) essential oil	20% oil solution	An. stephensi
	Sage (S. sclarea) essential oil	20% oil solution	An. stephensi
	C. longa essential oil	10%	An. dirus
	Confertifolin essential oil P. tuberosa extract	5 ppm 2%	An. stephensi An. stephensi
4 < to < 5	Clove oil Clove oil C. citratus extract Myrtle essential oil I. cairica essential oil	Cream 20% 20% gel 1/5 mg/cm2 50% 4%	An. dirus An. dirus An. arabiensis An. stephensi An. stephensi
4	C. longa essential oil	5%	An. dirus
	P. tuberosa extract	1.5%	An. stephensi

Stratification of potential of plant based repellents by complete protection times, up to July 2018

Citronella

The repellency effect of citronella was investigated in several studies. Citronella is an essential oil extracted from the stems and leaves of different species of lemongrass (Cymbopogon spp.) [65]. Ansari et al. [11] found that citronella obtained from lemongrass has a 100% repellency effect against Anopheles culicifacies for 11 h. Amer et al. [6] and Tawatsin et al. [44] also reported that citronella could repel Anopheles stephensi and Anopheles dirus for 8 and 6 h, respectively. Moreover, 100 μl and 0.1 ml of citronella grass essential oil showed 2.16 and 0.8 h complete protection time against An. minimus [45] and An. dirus [47], respectively. The percentage repellency of citronella in other studies. [6, 52, 59], depending on the concentration of extracts and Anopheles species, was reported to be 52 to 85%.

Peppermint

Peppermint is a hybrid mint from cross-breeding spearmint (Mentha spicata) and water mint (Mentha aquatica), which contains biologically active constituents and has high menthone, menthol and methyl esters. The plant, indigenous to Europe, is now widespread in cultivation worldwide [66]. The effect of peppermint on Anopheles was explored in 3 studies. Ansari et al. [12] in a field trial revealed that 1 ml peppermint oil without dilution completely repels Anopheles annularis, An. culicifacies and Anopheles subpictus for 11, 9.6 and 7.3 h, respectively and the corresponding percentage repellency were 100%, 92.3% and 83.1%. In another study [6], 20% oil solutions of peppermint had 57% repellency and complete protection time for 6.5 h against An. stephensi. The study by Sritabutra et al. [47] also found that 0.1 ml of peppermint essential oil protect against An. dirus for 1.08 h.

Cinnamomum

Cinnamomum is a genus in the Laurel family, Lauraceae, several of which are investigated for their antibacterial activity by means of essential oils from bark and leaves [67]. Amer et al. [6] reported that 20% oil solutions of both camphor (Cinnamomum camphora) and cinnamon (Cinnamomum zeylanicum) had 100% repellency affect against An. stephensi. While, in the study conducted by Govindarajan et al. [22], C. zeylanicum at 1 mg/cm2 showed 1 h protection against An. subpictus.

Catnip (Nepeta cataria)

Catnip is a perennial plant that belongs to the mint family, Labiatae. This herb is spread from central Europe to central Asia and the Iranian plateaus [68]. The 20% oil solution of catnip in the study carried out by Amer et al. [6], with 100% protection against An. stephensi for 8 h, had a good effectiveness in preventing Anopheles mosquitoes. Nevertheless, Birkett et al. [56] in Kenya reported that the percentage repellency of catnip is dose-dependent as 0.01 mg, 0.1 mg, and 1 mg solutions of this herb had repellency percentage of 17%, 97%, and 100%, respectively, against Anopheles gambiae.

Thyme (Thymus serpyllum)

Thyme is one of nine species belonging to T. serpyllum, a perennial aromatic plant of the Mediterranean flora [69]. Thymus species have been reported to possess various beneficial effects, such as antiseptic, carminative, antimicrobial, and antioxidant properties [70]. The 20% oil solution of thyme in the study conducted by Amer et al. [6], with 100% protection against An. stephensi for 7.5 h, had a good effectiveness in preventing Anopheles mosquitoes. Nevertheless, another study [58] reported that the complete protection time of thyme at its maximum concentration (100%) is 1.7 h against Anopheles albimanus.

Olive (Olea europaea)

Olive (O. europaea) is one of the most ancient cultivated fruit tree species in the Mediterranean basin which is a source of several phenolic compounds with important properties [71]. The 20% oil solution of olive in the study conducted by Amer et al. [6], with a mean percentage of repellency (71.4%) and complete protection time against An. stephensi for 8 h, had a good effectiveness in preventing An. stephensi mosquitoes. Karunamoorthi et al. [50] also supported that burning of 25 g of dried O. europaea, comparable to Amer et al. [6], has a percentage repellency of 79.7 against Anopheles arabiensis.

Eucalyptus

Eucalyptus is a significant short rotation pulpy woody plant, grown generally in tropical regions [72]. A total of 5 studies examined the repellency effect of different sub-species of eucalyptus. In the laboratory trial by Amer et al. [6], narrow-leaved eucalyptus, lemon-scented eucalyptus, and broad-leaved eucalyptus protected against An. stephensi for 8 h, while Eucalyptus globulus complete protection time was reported to be 5.5 h. Auysawasdi et al. [41] used E. globulus essential oil at 5%, 10%, 15%, 20% and 25% concentrations against An. dirus. All concentrations of E. globulus provided complete repellency ranging from 1.7 to 3.4 h, depending on the concentration applied. Eucalyptus globulus at 0.1 ml dose in a study [47] repelled An. dirus for 1.58 h. Besides, 100 μl Eucalyptus citriodora repelled An. minimus for 0.5 h [45]. In contrast, Seyoum et al. found that lemon eucalyptus extract is not affective against An. gambiae [54].

Myrtle (Myrtus communis)

Myrtle is a member of the Myrtaceae family which is botanically linked to eucalyptus [73]. In 2 studies, repellency effectiveness of myrtle was investigated. The 20% oil solution of myrtle in the study conducted by Amer et al. [6], with mean percentage repellency of 42.8% and complete protection time against An. stephensi for 6.5 h, had a good effectiveness in preventing Anopheles mosquitoes. Tavassoli et al. [62] also supported that myrtle at 50% concentration repels An. stephensi for 4.36 h.

Basil

Basil is an annual plant of the Ocimum genus, which belongs to the Lamiaceae family and is used in traditional medicine in many parts of the world [74]. In 6 studies, repellency effectiveness of basil against different Anopheles species was investigated. In the laboratory trial by Amer et al. [6], 20% oil solution of basil essential oil, with mean percentage repellency of 66.7%, had 100% protective impact against An. stephensi for 3.5 h. Phasomkusolsil et al. [42] used basil essential oil at 0.02, 0.10, and 0.21 mg/cm2 concentrations against An. dirus. The percentage repellency was dose–response and was reported to be 66%, 74% and 96%, respectively. Basil at 0.1 ml dose in other studies [47, 61] repelled Anopheles for 1.5 h and 0.75 h, whereas, Tawatsin et al. [44] found that hairy basil oil provides 100% protection against An. dirus for 6 h. In contrast, in the study by Seyoum et al. [54], no remarkable repellency effect against An. gambiae was identified.

Tagetes (Tagetes minuta)

Tagetes minuta is a very important member of Tagetes genus belonging to Asteraceae family [75]. In 2 studies, repellency effectiveness of tagetes was explored. The 20% oil solution of T. minuta in the study conducted by Amer et al. [6], with complete protection time for 8 h, had a good effectiveness in preventing against An. stephensi. In contrast, Seyoum et al. found that tagetes extract is not affective against An. gambiae [54].

Neem (Azadirachta indica)

Neem is a versatile tree broadly grown in tropical areas of India [76]. The repellency effect of Neem against different species of Anopheles was investigated in 2 studies. The 20% Neem oil in a field trial conducted by Amer et al. [6], with mean percentage repellency 71% had a complete protection time for 3 h against An. arabiensis. Nevertheless, Seyoum et al. found that Neem extract is not affective against An. gambiae [54].

Rosemary (Rosmarinus officinalis)

Rosemary is an evergreen aromatic shrub with a Mediterranean origin, which belongs to Lamiaceae (Labiatae) family [77]. In 2 studies, repellency effectiveness of rosemary was reported. The 20% oil solution of rosemary in the study conducted by Amer et al. [6], with 100% protection against An. stephensi for 8 h, had a good effectiveness in preventing Anopheles mosquitoes. Govindarajan et al. [22] also supported that rosemary at 1, 2.5 and 5 mg/cm2 concentrations completely repels An. subpictus for 1, 1, and 1.5 h, respectively.

Clove (Syzygium aromaticum)

Clove is a naturally occurring spice which has been shown to possess anti-bacterial, anti-oxidant, anti-pyretic, anti-candidal, and aphrodisiac activities [78]. The repellency effect of clove against different species of Anopheles was investigated in 6 studies. In the study by Phasomkusolsil et al. [42], clove at 0.02, 0.10 and 0.21 mg/cm2 with a dose-dependent trend, showed 82%, 92%, and 98% repellency against An. dirus. Barnard et al. [58] used clove essential oil at 25%, 50%, 75%, and 100% concentrations against An. albimanus and found that all concentrations of clove provided complete repellency ranging from 1.25 to 3.55 h, depending on the concentration applied. Consistently, clove at 10%, 50%, and 100% concentrations, with a dose-dependent trend, showed 1.33, 2.66, and 3.5 h complete repellency against An. dirus [43]. Anopheles dirus was repelled by clove for 1 h in laboratory conditions in Thailand [47]. Another study [45] reported that clove repels An. minimus for 2 h. Moreover, 20% gel of clove protected against An. dirus for 4.5 h [46]. All these findings support that clove can be a considered as moderate repellent.

Orange oil (Citrus sinensis)

Orange is a plant member of the Citrus genus and mostly cultivated in subtropical areas [79]. The repellency effect of orange against different species of Anopheles was investigated in 4 studies. In the study by Murugan et al. [27], orange extract at 50, 150 and 250, 350, and 450 ppm showed 0, 0.5, 0.5, 1.5 and 2 h complete protection time repellency (100%) against An. stephensi, respectively. While, in another study [45], it repelled An. minimus for 0.83 h. Similarly, Sritabutra et al. [47] showed that orange repels An. dirus for 0.83 h. Phasomkusolsi et al. [42] also found that orange at 0.02, 0.10, and 0.21 mg/cm2, with a dose-dependent trend, has 44%, 54%, and 84% repellency against An. dirus, respectively.

Turmeric (C. longa)

The medicinal plant turmeric, which is a perennial herb, and a member of Zingiberacae family, is commonly used as a spice in human food [80]. In 3 studies, repellency effectiveness of turmeric was examined. Auysawasdi et al. [41] used turmeric essential oil at 5%, 10%, 15%, 20%, and 25% concentrations against An. dirus. All concentrations of turmeric, with a dose–response manner, provided complete repellency ranging from 4 to 8 h, depending on the concentration applied. Other studies also found that turmeric oil repels An. dirus for 6 h [44] and An. minimus [45] for 1 h.

Discussion

A high level of insecticide resistance has made because of the chemical control of the pests and vectors. To overcome this problem, it is essential to research for alternative approaches to vector control. The field of herbal repellents is extremely fertile as people demand mosquitoes’ repellents that are safe, pleasant to usage and ecologically maintainable. As cost is a significant factor, examination of the use of local florae as repellents is highly suggested. Essential oils and extracts of plants are emerging as potential agents for Anopheles spp. control, with easy-to-administer, low-cost, and risk-free properties. In the present systematic review the highest repellency effect against Anopheles mosquitoes was found from L. sinense extract, followed by citronella, pine, D. sissoo, peppermint and R. mucronata oils with complete protection time ranging from 9.1 to 11.5 h. Essential oils from plants such as lavender, camphor, catnip, geranium, jasmine, broad-leaved eucalyptus, lemongrass, lemon-scented eucalyptus, amyris, narrow-leaved eucalyptus, carotin, cedarwood, chamomile, cinnamon oil, juniper, cajeput, soya bean, rosemary, niaouli, olive, tagetes, violet, sandalwood, litsea, galbanum, and C. longa also showed good repellency with 8 h complete repellency against different species of Anopheles genus.

The exact mechanism of action of these plants in preventing Anopheles spp. bites has not yet been completely clarified. For citronella, as one of the most explored plant for repellency effect against various mosquitoes, it is reported that active compounds in citronella extract for repelling mosquitoes are eugenol, eucalyptol, camphor, linalool, citral, and citronellal [81]. Some data proposes that these agents interfere with olfactory receptors of mosquitoes [82]. A recent study revealed that An. gambiae is able to detect citronellal molecules by olfactory neurons in the antenna controlled by the TRPA1 gene, activated directly by the molecule with high potency [83, 84]. Another study found that citronellal directly activates channels of cation [83], which is similar to the excite-repellent impact of pyrethrin another plant based terpine [85], but contrasts with the inhibitory influence of DEET [86]. Although the protection time of citronella oil is shorter than that of DEET. Citronella oil could provide sufficient protection time against mosquitoes. For other plants, the underlying mechanism remains to be elucidated. Possibly, the most important aspect in increasing the permanence of such repellents that are effective but volatile is improving formulations of plant extracts to elevate their longevity through the development of nanoemulsions, improved formulations, and fixatives. While alternative uses such as excite-repellency and spatial activity have also been examined [87].

Some caution is important when interpreting the findings. First, a poorly inspected confounding aspect is the effect of sweating on the effectiveness and protection time of repellents, which are approximately all water-soluble, and this might limits the comparability of repellents. Second, in field trial studies, the number of human volunteers as well as the season during which the trial had been performed differed among the included studies. Climate could also affect mosquito behaviour and the variance is controlled by standardizing humidity temperature in ‘arm-in-cage’ trials; however, these parameters are not always similar in different trials or conform to the mosquito environment standards. Third, it should be highlighted that some plant compounds are irritating to the skin and/or highly toxic to mammals, and natural does not equate to safe. Thus, plants with potential repellency properties should be tested for their possible unpleasant side effects before introducing as alternative products. Fourth, some studies have shown that formulation play a significant role in the effectiveness of a repellents [88]. However, studies have focused more on the search for active compounds than on optimal formulations [8, 29]. Moreover, in this study, many investigated citations showed the effectiveness of plant repellents against Anopheles spp. mosquitoes. However, when focusing on Anopheles subspecies, there were only a few publications indicating the efficacy of each plant, which resulted in a difficulty to reach a robust conclusion regarding the best herbal candidates to develop new commercial repellents.

This is another area for additional research. Finally, current studies are difficult to be compared and the repellency effectiveness may also differ among subspecies. Unfortunately, a few studies aimed to compare repellency efficacy of a special plant on subspecies of Anopheles. The heterogeneity in the results of the previous studies might be stem from differences in compound concentrations, application dosages, mosquito species, formulations and the assessment method of repellency, as in some trials the protection time until mosquitoes landed was recorded, whereas in the majority of studies the time until mosquitoes bite was considered. Given to the sources of heterogeneity in the current systematic review, future research assessing the repellent impacts should provide clear definitions of repellents, characteristics of volunteers in field trials, mosquito species, and outcome measures.

Conclusion

The results of this study showed that some plants essential oils and extracts have significant repellent activity against Anopheles spp. mosquitoes. The studies in the last two decades have focused on the search for new natural repellents and some plants displayed good repellent activities, but few natural products have been developed so far [88, 89]. This review calls for the attention of entomologists and people in the field of mosquito-transmitted diseases for understanding the value and potential position of the plant-derived repellents and their role in disease control.