A review on Hyalomma species infestations on human and animals and progress on management strategies

Abstract

The Hyalomma species of ticks have gained additional attention due to their role in the transmission of Theileria annulata infection in animals and the Crimean-Congo Haemorrhagic Fever (CCHF) virus in humans. Apart from these, many other pathogens viz., other species of Theileria, a few species of Babesia, Rickettsia and viruses are either maintained or transmitted by this tick species. The medium to large size species with longer proboscis has inflicted additional burden on the overall impact of tick infestations. Being a multi-host species, management of the species is very challenging. Presently, the traditional method of tick management using chemical acaricides is found insufficient and unsustainable. Henceforth, the overall burden of tick infestations and tick-borne diseases are increasing gradually. After the successful development of vaccines against cattle tick, Rhipicephalus microplus, the anti-Hyalomma vaccine is considered a feasible and sustainable management option. In the recent past research on herbal acaricides and its possible application for tick control seems promising. Other eco-friendly methods are still under experimental stage. The present review is focused on impact of Hyalomma species infestation on human and animal health with special emphasis on progress on its sustainable management.

Hyalomma species; Tick-borne pathogens; Acaricide resistance; Immunoprophylaxis; Phytoformulation; Zoonoses; Agricultural science; Environmental science;Veterinary medicine; Veterinary science

1. Introduction

Globally, ticks and tick-borne diseases (TTBDs) are the major hurdles to enhance livestock productivity with the threshold being much higher in developing countries. The cumulative global losses incurred for the management of TTBDs are estimated at the tune of US $ 22–30 billion per annum (Minjauw and Mc Leod, 2003; Lew-Tabor and Rodriguez-Valle, 2016). The direct effect of tick infestations on hosts includes pyemia, toxicosis and paralysis which cause a cumulative projected loss of about US $ 500 million annually (Minjauw and Mc Leod, 2003; Chhillar et al., 2014). In addition, production losses due to tick infestations with respect to growth and milk production were estimated as 8.9 ml of milk and 1 g live weight gain per engorging female tick per day, respectively (Jonsson et al., 2001). Recently, due to climate change and other risk factors, TTBDs have risen insidiously, triggering heightened attention about their impact on human health. In concurrence to this, the Centre for Disease Control and Prevention (CDC) reported nearly doubling of TTBDs cases over 13 years (Rosenberg et al., 2018).

The ixodid tick species of the genus Hyalomma have major medical and veterinary significance in terms of health and economic impediment in the tropical and subtropical regions (Bakheit et al., 2012). The natural distribution of Hyalomma species is limited to Asian, African and European continents (Sands et al., 2017). Out of the 27 valid species of Hyalomma (Guglielmone et al., 2010), five species are widely distributed and recorded in all the three continents, seven species are restricted in Asia, five in Africa, nine in Asia-Africa and one in Africa-Europe. About 50% of the species can infest and transmit pathogens, most significantly, the Crimean Congo Haemorrhagic Fever (CCHF) virus in humans (Verma et al., 2011; Hornok and Horváth, 2012; Aktas et al., 2014; Gargili et al., 2017) and Theileria annulata in cattle (Robinson, 1982; Dumanli, 1989). Apart from that, Hyalomma species are also known for the maintenance and transmission of many other viruses, bacteria and protozoan pathogens to animals and humans.

Repeated applications of chemical acaricides are the backbone of tick management having limited efficacy (Chema, 1990; Pegram et al., 1991, 1993; Meneghi et al., 2016). The approach based on acaricide application suffers from many drawbacks such as repetition of applications, environmental pollution, acaricide residues in livestock products, selection of resistant ticks, non-availability of new generation acaricides in near future and high cost of development of new generation acaricides (de la Fuente and Kocan, 2006). It has been estimated that the cost of discovering and developing a novel product is around the US $ 100 million, with an average time requirement is 10 years (Graf et al., 2004). These issues enforced the scientific community to develop and introduce alternatives to acaricides that are consistent with the principles of sustainable TTBDs management (Willadsen, 2006; de la Fuente and Kocan, 2006; Merino et al., 2011; Ghosh et al., 2013). The alternative approaches are strategic use of effective acaricides; adoption of the resistance monitoring system for identification of zone-specific effective acaricides; biological control; use of phytoformulation; vaccines. The present review is focussed on direct and indirect impact Hyalomma ticks and its possible management strategies.

2. Impact of Hyalomma tick on human beings

Many species of Hyalomma are recorded from human and considered as zooanthrophilic, occasionally feed on a human. Apart from many unreported cases of human- Hyalomma association, some cases are well documented viz., H. marginatum (Keirans and Durden, 2001) and H. truncatum (Apanaskevich and Horak, 2008; Mathison et al., 2015). Many times tick bites are unrecognized but it may cause itching, pain, inflammation, redness and swelling at the site of the bite. Hyalomma species are also been involved in otoacariasis and tick paralysis in humans, for example, H. brevipunctata, H. marginatum, H. isaaci and other species of Hyalomma were recovered from patients having facial nerve paralysis, ear pain, swelling and inflammation around the ear (Edussuriya and Weilgama, 2003; Dilrukshi et al., 2004; Gurbuz et al., 2010; Doğan et al., 2012).

After mosquitoes, ticks are considered as the second most important arthropod vector in the transmission of pathogenic agents. In human, Hyalomma ticks act as vector of CCHF virus (Turell, 2007). Worldwide, CCHFV has been reported in 15 species of Hyalomma viz., H. aegyptium, H. anatolicum, H. asiaticum, H. dromedarii, H. excavatum, H. impeltatum, H. impressum, H. lusitanicum, H. marginatum, H. nitidum, H. rufipes, H. schulzei, H. scupense, H. truncatum and H. turanicum along with other ticks species through PCR/RT-PCR identification and/or by inoculation tick extract in mice (Gargili et al., 2017). At least eight species of Hyalomma such as H. marginatum, H. dromedarii, H. rufipes, H. anatolicum, H. asiaticum, H. truncatum, H. turanicum and H. impeltatum were recognized as potential vector competence for acquiring, maintenance and transmission of CCHFV (Bakheit et al., 2012; Mourya et al., 2012; Gargili et al., 2017; Deka, 2018; Spengler and Estrada-Peña, 2018). The CCHF is an acute, often fatal hemorrhagic fever (VHF) and the reported case fatality rate is 3 % to >30% (Ergonul, 2006; Yadav et al., 2016; Al-Abri et al., 2017; Gargili et al., 2017). The disease is endemic in Africa, Asia, Eastern Europe, and the Middle East and few sporadic outbreaks were also recorded in Kosovo, Albania, Iran, and Turkey. Recently, the westward expansion of the virus in Europe has been observed through detection of CCHFV in ticks and autochthonous human cases in Spain (Estrada-Peña et al., 2012; Negredo et al., 2017; Oteo and Palomar, 2018). During the last one decade, most of the outbreaks were reported from Pakistan, Iran, Sudan, India and Bulgaria (Whitehouse, 2004; Aradaib et al., 2010; Patel et al., 2011; Messina et al., 2015; Akuffo et al., 2016; Al-Abri et al., 2017; Dowall et al., 2017). Apart from CCHFV, other zoonotic important viruses and bacteria were also recorded sporadically in Hyalomma ticks in limited geographical areas (Table 1). But, further studies are to be done to define the vector competence and relationship between the geographic distributions of these ticks and pathogens. In Saudi Arabia, Al-Khalifa et al. (2007) reported various zoonotic viruses from different Hyalomma species like Sindbis in H. dromedarii and H. impeltatum; Chick Ross in H. dromedarii; Kadam in H. dromedarii and H. anatolicum and Dhori in H. impeltatum and H. schulzei but transmission potential of these species has not been confirmed. Bhanja virus, a member of family Phenuiviridae (Order: Bunyavirales) is transmitted to vertebrates through biting arthropods including ticks (Matsuno et al., 2013). It was first isolated from Hemaphysalis intermedia and later from different species of Hyalomma (Table 1) responsible for causing sporadic cases of febrile illness and encephalitis in humans (Vesenjak-Hirjan et al., 1980; Hubalek, 2009). Seroprevalence of Kadam virus in human and recognition of virus in H. dromedarii may be correlated but with a precaution that both the events are reported at two different geographical locations (Wood et al., 1982). Further, the Thogoto and Dhori viruses (family: Orthomyxoviridae) cause severe illness and even death in humans. Primarily, it is a 'tick-borne virus' but aerosol transmission could also possible in humans (Peng et al., 2017). Dhori viruses may cause a disease similar to avian influenza (H5N1) in humans (Li et al., 2008). The West Nile virus is mainly transmitted through mosquitoes and cause mild to severe disease with the involvement of brain (encephalitis) but the virus was also isolated from tick, H. marginatum collected from animals and birds (L'Vov et al., 2002; Oehme et al., 2017) and vector capacity of H. marginatum was established experimentally (Formosinho and Santos-Silva, 2006). Similarly, Venezuelan equine encephalitis virus (family: Togaviridae) is responsible for causing serious disease in horses and humans. The mosquitoes are the principal vector but experimental transmission of the virus through H. truncatum was also reported (Linthicumlt and Logan, 1994).

Table 1.

Zoonotic pathogens of public health importance transmitted and/or maintained by Hyalomma species.

Pathogens	Hyalomma species	Countries where pathogens detected in Hyalomma tick
Crimean-Congo Haemorrhagic Fever (CCHF) virus	H. marginatum (Jameson et al., 2012; Gargili et al., 2017; Duscher et al., 2018) H. anatolicum (Tajeri and Razmi, 2011; Gargili et al., 2017) H. asiaticum (Teng and Jiang, 1991) H. dromedarii (Hoogstraal et al., 1981) H. rufipes (Hornok and Horváth, 2012; Gargili et al., 2017) H. truncatum (Linthicumlt and Logan, 1994; Gargili et al., 2017) H. turanicum (Gargili et al., 2017) H. impeltatum (Bakheit et al., 2012)	Africa, Asia and Europe. like Crimea, Astrakhan, Rostov, Uzbekistan, Kazakhstan, Tajikistan, Democratic Republic of the Congo, Uganda, Mauritania, Iraq, the United Arab Emirates, Saudi Arabia, Pakistan, Iran, Bulgaria, Turkey, Russia, Spain and India (Whitehouse, 2004; Aradaib et al., 2010; Patel et al., 2011; Estrada-Peña et al., 2012; Messina et al., 2015; Akuffo et al., 2016; Al-Abri et al., 2017; Dowall et al., 2017; Negredo et al., 2017)
Dhori virus	H. marginatum H. dromedarii (Hoogstraal et al., 1981; Labuda and Nuttall, 2004; Lledó et al., 2020); H. impeltatum and H. schulzei (Al-Khalifa et al., 2007)	Egypt (Williams et al., 1973), Saudi Arabia (Al-Khalifa et al., 2007), Portugal, Russia (Lledó et al., 2020)
Kadam virus	H. dromedarii and H. anatolicum (Wood et al., 1982; Al-Khalifa et al., 2007)	Kenya, Uganda (Wood et al., 1982), Saudi Arabia (Wood et al., 1982; Al-Khalifa et al., 2007)
Sindbis virus	H. dromedarii and H. impeltatum (Al-Khalifa et al., 2007)	Saudi Arabia (Al-Khalifa et al., 2007)
Chick Ross virus	H. dromedarii (Al-Khalifa et al., 2007)	Saudi Arabia (Al-Khalifa et al., 2007)
Thogoto virus	Hyalomma spp. (Labuda and Nuttall, 2004; Mueller and Lormeau, 2018), H. dromedarii, H. rufipes (Kazimírová et al., 2017), H. nitidum (Lledó et al., 2020)	Egypt, Nigeria (Mueller and Lormeau, 2018), Central African Republic (Lledó et al., 2020)
West Nile virus	H. marginatum (L'Vov et al., 2002; Formosinho and Santos-Silva, 2006; Oehme et al., 2017)	Russia, Portugal (L'Vov et al., 2002; Formosinho and Santos-Silva, 2006)
Bhanja virus	H. marginatum, H. detritum, H. dromedarii, H. truncatum and H. asiaticum (Hubalek, 2009)	Central and southern Europe (Hubalek, 2009)
Venezuelan equine encephalitis virus	H. truncatum (Linthicumlt and Logan, 1994)	Experimental transmission study (Linthicumlt and Logan, 1994)
Rift Valley Fever virus	H. truncatum (Nchu and Rand, 2013)	Experimental transmission study (Linthicum et al., 1989), Africa (Nchu and Rand, 2013)
Anaplasma phagocytophilum	H. aegyptium (Pastiu et al., 2012)	Romania (Pastiu et al., 2012)
Ehrlichia canis	H. aegyptium (Pastiu et al., 2012)	Romania (Pastiu et al., 2012)
Coxiella burnetii	H. aegyptium (Pastiu et al., 2012) H. dromedarii (Rehácek and Brezina, 1968) H. scupense (Goddard, 2012) H. truncatum (Capponi et al., 1970)	Experimental transmission study (Rehácek and Brezina, 1968; Siroký et al., 2010), Senegal (Capponi et al., 1970), Romania (Pastiu et al., 2012)
Rickettsia aeschlimannii	H. aegyptium (Bitam et al., 2009), H. dromedarii (Demoncheaux et al., 2012), H. marginatum, H. scupense, H. truncatum, H. rufipes, H. ditritum, H. impeltatum, H. exavatum (Beati et al., 1997; Demoncheaux et al., 2012; Kumsa et al., 2015; Duscher et al., 2018)	Africa (Morocco, Zimbabwe, Niger, Mali, Algeria, Senegal, Ethiopia, Chad, Egypt, Sudan, Tunisia), Europe (Russia, Italy, France, Croatia, Portugal, Greece, Spain, Georgia, Germany, Turkey, Austria (Bitam et al., 2009; Demoncheaux et al., 2012; Duscher et al., 2018)
R. sibirica	H. asiaticum, H. excavatum, H. truncatum, H. turanicum, H. marginatum (Parola et al., 2001; Psaroulaki et al., 2005; de Sousa et al., 2006; Kleinerman et al., 2013; Keskin and Bursali, 2016)	Mongolia, Niger, Greece, Cyprus, Israel and Turkey (Parola et al., 2001; Psaroulaki et al., 2005; de Sousa et al., 2006; Kleinerman et al., 2013; Keskin and Bursali, 2016)
R. conorii	H. albiparmatum (Heisch et al., 1962), H. rufipes, H. truncatum (Mathison et al., 2015)	Kenya (Heisch et al., 1962)
R. rickettsii	H. dromedarii (Mohamed, 2000)	----
R. africae	H. impeltatum (Parola et al., 2013), H. dromedarii (Kernif et al., 2012), H. aegyptium (Gargili et al., 2012) H. marginatum (Wallménius et al., 2014)	Algeria, Egypt, Turkey, Italy, Greece (Abdel-Shafy et al., 2012; Kernif et al., 2012; Gargili et al., 2012; Wallménius et al., 2014)
Borrelia turcica	Hyalomma aegyptium (Kalmar et al., 2015)	Romania (Kalmar et al., 2015)

Tick-borne rickettsioses are recognized as emerging/reemerging zoonotic infections worldwide. Rickettsia aeschlimannii was first isolated from H. marginatum and characterized as spotted fever group rickettsia (Beati et al., 1997), later, it was detected in many other Hyalomma species. Other rickettsias of spotted fever group such as R. sibirica, R. conorii, R. rickettsii and R. africae were also isolated from various species of Hyalomma but the vector capacity of these species has not been confirmed (Nicholson et al., 2009). Similarly, Coxiella burnetii, Anaplasma phagocytophilum and Ehrlichia organisms were detected in Hyalomma but its vector competency has not yet been established. A spirochetes bacteria, Borrelia turcica, a reptile-associated borreliae, has been identified in H. aegyptium and tortoise which may be zoonotic though its pathogenicity is unknown (Kalmar et al., 2015).

3. Impact of Hyalomma ticks on animals

Hyalomma ticks are medium to large in size and have long mouthparts through which the species cause tissue damage and predispose conditions for myiasis and tick pyaemia. Though Hyalomma may cause significant impact through its painful bite, sucking of the large volume of blood leading to anaemia, tick worry and annoyance affecting the productivity of the animals but these parameters are rarely quantified. According to Balashov (1972), H. asiaticium may take about 8.856 ml of blood for repletion. Sajid et al. (2007) assessed the direct effect of Hyalomma ticks on animal productivity and reported an average daily increase of 1.15 L in milk yield per animal with 1.31 % more fat in acaricide-treated animals compared to Hyalomma infested animals. Moreover, the salivary toxin may cause dermatitis, paralysis and lameness viz., bites of H. asiaticum and H. truncatum cause lameness to lambs (Azizi and Yakhchali, 2006) and sweating sickness in animals (Jongejan and Uilenberg, 2004).

Besides these, Hyalomma ticks are transmitting and/or maintaining a number of bacterial, viral and protozoan pathogens (Bakheit et al., 2012). The major haemoparasitic pathogens causing babesiosis, theileriosis, and anaplasmosis in cattle are transmitted by the tick species and the economic impact of the diseases in the cattle production system is very high (Minjauw and Mc Leod, 2003; Jongejan and Uilenberg, 2004). Although Hyalomma species are not normally involved in the transmission of major pathogenic species of Babesia viz., B. bigemina, B. bovis, B. divergens and B. major but recently few genetically distinct Babesia like Babesia U sp., Babesia sp. Kashi 1 and 2, Babesia sp. Kayseri 1, Babesia sp. CS58, Babesia sp. Hy, B. beliceri and B. ocultans are recorded from Hyalomma spp. (Table 2). The equine piroplasmosis, an economically significant disease of equines, caused by B. caballi and T. equi are also transmitted by Hyalomma (H. truncatum, H. anatolicum). Similarly, different species of Theileria viz., T. annulata, T. lestoquardi, T. ovis, T. equi and T. camelensis are also transmitted by Hyalomma spp. (Geevarghese and Dhanda, 1987; Lewis et al., 2005; Li et al., 2010). These haemoprozoans have mild to severe impact on animal productivity. Apart from haemoprotozoans, Hyalomma ticks are also maintained and/or transmit zoonotic rickettsial pathogens viz., R. aeschlimannii, C. burnetii, R. conorii, R. sibirica, R. africae, A. phagocytophilum, A. marginale, A. ovis, A. central and Ehrlichia canis to animals (Losos, 1986; Aubry and Geale, 2011; Bakheit et al., 2012; Goddard, 2012) (Table 2) but the tick species of the genus does not denote its active involvement in the transmission and/or maintenance of these pathogens in natural cycles. For most of these rickettsial pathogens, animals act as symptomless carrier/reservoir but some of the pathogens cause mild to severe diseases like Q-fever in ruminants caused by C. burnetii, granuloctic Anaplasmosis in livestock by A. phagocytophilum, Erythrocytic Anaplasmosis in ruminants by A. marginale and A. ovis and Canine Ehrlichiosis by E. canis in animals.

Table 2.

List of pathogens of veterinary importance transmitted and/or maintained by Hyalomma species.

Hyalomma spp.	Pathogens list I#	Pathogens list II##
H. aegyptium	Theileria annulata (Ray, 1950) Hepatozoon kisrae (Paperna et al., 2002) Hemolivia mauritanica (Paperna, 2006) Coxiella burnetii (Siroký et al., 2010)	Anaplasma phagocytophilum and Ehrlichia canis (Pastiu et al., 2012) Borrelia turcica Sp. Nov. (Güner et al., 2004) Borrelia burgdorferi s.l. and Rickettsia spp. (Kar et al., 2011) T. lestoquardi (Vashishta et al., 1987)
H. anatolicum	Theileria annulata (Dhar et al., 1982; Lewis et al., 2005; Ica et al., 2007; Li et al., 2010) T. equi (Bhattacharyulu et al., 1975; Li et al., 2010), T. lestoquardi (Uilenberg, 1997; Kirvar et al., 1998; El-Azazy et al., 2001; Khalid and ElHussein, 2010), T. ovis (Li et al., 2010)	Babesia spp. (Guan et al., 2009), Babesia U spp. (Luo et al., 2003), B. beliceri (Chaudhuri et al., 1975), Karyana and Kundal viruses (Yadav et al., 2019)
H. dromedarii	T. annulata (Samish and Pipono, 1978; Ica et al., 2007) T. camelensis (Hoogstraal et al., 1981)	C. burnetii (Hoogstraal et al., 1981)
H. excavatum	T. lestoquardi (Hashemi-Fesharaki, 1997) A. marginale and A. centrale (Shkap et al., 2009)	T. annulata (Abdel-Shafy and Zayed, 2002; Aktas et al., 2004)
H. impeltatum	B. ocultans (Dipeolu &Amoo, 1984) T. lestoquardi (El-Azazy et al., 2001)
H. imperessum	B. ocultans (Dipeolu and Amoo, 1984)
H. lusitanicum		A. phagocytophilum (Kumsa et al., 2015)
H. marginatum	B. ocultans (Dipeolu and Amoo, 1984), T. annulata (Aktas et al., 2004; Samish and Pipono, 1978; Estrada-Pena et al., 2004)	Babesia sp. Kashi 1 and 2, Babesia sp. Kayseri 1, Babesia sp. CS58, Babesia sp. Hy (Aktas et al., 2014)
H. rufipes	B. ocultans (Gray and De Vos, 1981; Dipeolu and Amoo, 1984)
H. scupense	T. annulata (Samish and Pipono, 1978; Aktas et al., 2004; Ica et al., 2007)	C. burnetii (Goddard, 2012)
H. truncatum	B. ocultans (Dipeolu and Amoo, 1984) B. caballi (Blouin and de Waal, 1989) Rift Valley Fever virus (Nchu and Rand, 2013) Venezuelan equine encephalitis Virus (Linthicumlt and Logan, 1994)	C. burnetii (Hoogstraal et al., 1981) Bhanja, Dugbe and Jos viruses (Hoogstraal et al., 1981)

Note:^#Pathogens detected in Hyalomma tick and transmission potentials have been confirmed. ^##Pathogens detected in Hyalomma tick but transmission potentials have been not confirmed.

Almost all the viruses discussed under the heading 2 (Impact of Hyalomma tick on Human beings) are zoonotic, maintained in ticks and non-human vertebrate animals. Many other viruses have been isolated from the Hyalomma spp. infesting animals viz., Kadam, Chick Ross, Sindbis and Wanowrie viruses (Williams et al., 1973; Al-Khalifa et al., 2007), but the potentiality of the tick species as an efficient biological vector has not been established.

Overall the direct and indirect impact of Hyalomma ticks on human and animal health is considerably high. An estimated control cost of US$ 239.5 million alone due to bovine tropical theileriosis (Minjauw and Mc Leod, 2003) has been projected for India. Moreover, control cost of ticks through chemicals and its consequences in the society posing serious challenges before the scientific community to develop country-specific strategies.

4. Management of Hyalomma species

4.1. Mechanical/Physical intervention

As a traditional practice, the animals are groomed to dislodge ticks from the body and are then killed mechanically through crushing, burning or dipping in insecticides/oils. This approach has many limitations especially for multi-host ticks where the collection of feeding larvae and/or nymphs from animals is very difficult. In addition to this, larvae and nymphs have weak host specificity (Nava and Guglielmone, 2013; Espinaze et al., 2015) can feed on rodents, birds etc. and are transmitting deadly pathogens to humans. The hand-picking and mechanical killing of ticks without taking proper biosafety precautions is not advisable.

4.2. Use of chemicals

Out of the existing tick management platforms, use of chemical acaricides form the backbone of the programme due to easy availability and application. The commonly available acaricides are organophosphates (OP) (chlorfenvinphos, chlorpyrifos, coumaphos and diazinon), synthetic pyrethroids (SP) (cypermethrin, deltamethrin, flumethrin, permethrin), amidines (amitraz) and phenylpyrazole (fipronil) etc. After the introduction of injectable/parenteral endectocides, macrocyclic lactones (ML), avermectin (Ivermectin, Doramectin) and milbemycin (Moxidectin) compounds, the use of MLs is increased significantly for the management of endo and ectoparasites. Consequent to the indiscriminate usage of acaricides, resistant tick populations have been developed and established (FAO, 2004; Li et al., 2004; Jonsson and Hope, 2007; Perez-Cogollo et al., 2010; Fernandez-Salas et al., 2012; Shyma et al., 2012; Kumar et al., 2014; Singh and Rath, 2014; Jyoti et al., 2016; Nandi et al., 2018). Both Hyalomma and Rhipicephalus species are simultaneously infesting same animals, but due to the change in life cycle pattern (multi-hosts) of former species, the resistance development was reportedly less in comparison to Rhipicephalids (Wharton and Roulston, 1970; Sangwan et al., 1993; Shyma et al., 2012; Singh et al., 2013; Nandi et al., 2015; Jyoti et al., 2015). In a comprehensive study, Shyma et al. (2012) reported level-I resistance to deltamethrin [Resistance factor (RF) = 1.79–4.62] in nine isolates and to cypermethrin in 10 isolates while resistance to diazinon was detected in six isolates out of 20 isolates collected from three agro-climatic regions of India. Singh et al. (2015) recorded cypermethrin and amitraz resistance while Gaur et al. (2016) recorded resistance to deltamethrin and diazinon in isolates collected from Punjab and Rajasthan states. Kumar et al. (2016) studied acaricide resistance in isolates collected from 10 districts of Rajasthan against deltamethrin, cypermethrin, diazinon through adult immersion test (AIT) and larval packet test (LPT) and concluded that Hyalomma ticks are developing resistance where intensive crossbred cattle population are reared and SP and OP compounds are used for the management of tick populations.

4.3. Biological control

Naturally, ticks have relatively few enemies, but the use of predators, parasites and pathogens viz., bacteria, fungi, spiders, ants, beetles, rodents, birds and other living organisms have been documented to limit tick populations. Amongst the 96 commercially active ingredients listed against pests based on microorganisms, 33 and 36 active ingredients are bacteria and fungi, respectively, and eight are entomopathogenic nematodes (Samish et al., 2004). The pathogenic effect of active ingredients of bacteria against ticks has been reported. For example, Brown et al. (1970) observed the pathogenic effect of Proteus mirabilis, a gram-negative bacterium on Dermacentor andersoni. Further, Hendry & Rechav (1981) reported a detrimental effect of R. decoloratus extracts containing bacteria (Proteus spp., Klebsiella pneumoniae, Pseudomonas spp., P. mirabilis and Staphylococcus spp.) on H. marginatum and on other ticks. Hassanain et al. (1997) studied the efficacy of spraying three commercial varieties of Bacillus thuringiensis (B. thuringiensis kurstaki, B. thuringiensis israelensis and B. thuringiensis thuringiensis) against adults of H. dromedarii. Among the three varieties, the LC50 of B. thuringiensis kurstaki (1200–2344 mg/ml) was most pathogenic against H. dromedarii. The eggs of both the tick species were highly susceptible to the bacterial infection. Researchers so far reported 20 natural fungal species, of which, the efficacy of Beauveria and Metarhizium species against ticks is well documented (Abdigoudarzi et al., 2009). Under the laboratory conditions, it was reported that R. microplus and H. excavatum larvae are more susceptible to 12 fungal strains than R. sanguineus larvae. However, engorged R. microplus and R. sanguineus females were more susceptible to entomopathogenic fungi in comparison to H. excavatum females (Gindin et al., 2003). Further, 100% susceptibility of eggs to fungi were also reported (Gorshkova, 1966; Monteiro et al., 1998; Kaaya, 2000). Elham et al. (2013) studied the effect of Scopulariopsis brevicaulis fungal spore suspension and culture filtrate on larvae, nymphs and adults of H. anatolicum and high mortality of larvae and reduced biotic potential of the adults was reported. Sun et al. (2011) collected 13 species of entomopathogenic fungi from different areas in China and reported <90% efficacy of B. bassiana (B.bAT01, B.bAT17) and M. anisopliae strains against H. anatolicum.

El-Sadawy and Habeeb (1998) studied the effect of five strains of entomopathogenic nematode (EPNs); Steinernema spp. on H. dromedarii engorged nymphs and reported strain S1 has a lethal effect after 7-day post infestation. Similarly, the lethal effect of IS-5 strain of Heterorhabditis indicus was reported on both engorged nymphs and unfed adults of H. excavatum at a concentration of 250 nematodes/cm² within 2–3 days (Samish et al., 1999, 2000). El-Sadawy et al. (2008) studied two families of EPNs; Heterorhabditidae and Steinernematidae against H. dromedarii and higher efficacy of Heterorhabditid strains (12–92%) than Steinernematid strains (4–88 %) were recorded. Although promising results were reported in in vitro conditions, the in vivo efficacy data is almost non-existing. There is a need to have research collaboration between laboratories involved in the exploration of biocontrol agent and tick experts to establish the in vivo efficacy of the biocontrol agent as a part of the integrated tick management (ITM).

4.4. Phytoformulation

Literature reveals about 356 species of plants belonging to 105 families have been evaluated against 31 tick species worldwide. In most of the cases R. microplus was used as model parasite in in-vitro model and the subject has been reviewed time to time (Benelli et al., 2016; Wanzala, 2017; Nwanade et al., 2020). Due to the vastness of the subject and the focused area of the present review, the results obtained by different groups is tabulated in Table 3. As observed in the case of R. microplus, a number of solvent guided extracts and essential oils were extracted from aerial parts of different plants and very high level of antitick activity up to 100% was recorded. In general, plant-derived products are having many advantages over the chemical acaricides such as low mammalian toxicity, short environmental persistence and complex chemistry that limit the development of resistance against them (George et al., 2014). But, along with advantages, plant products are also having drawbacks such as variable efficacy, chemically less-stable and limited residual activity, often due to photosensitivity or high volatility (George et al., 2014).

Table 3.

List of plants evaluated for acaricidal/repellent properties against Hyalomma species.

Name of plant	Part of plant and solvent used	Ticks species	In-vitro efficacy	References
Artemisia herba alba Asso (Asteraceae)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 0.0296 μg/μl (DE), 0.0022 μg/μl (EA), 0.369 μg/μl (hexane) and 0.018 μg/μl (ethanol)	Abdel-Shafy et al., 2007
A. herba alba (Asteraceae)	aerial parts	H. aegyptium	LC50 = 1.105 (eggs), 0.755 (larvae) and 0.0079 μL/mL (nymphs)	Laghzaoui et al., 2018
A. monosperma Del. (Tarragon)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 0.0952 μg/μl (DE), 0.0636 μg/μl (EA), 0.0437 μg/μl (hexane) and 0.252 μg/μl (ethanol)	Abdel-Shafy et al., 2007
Azadirachta indica (Meliaceae)	NeemAzal F (Commercial product prepared from seed)	H. excavatum	Significant decrease in eggs hatching rate; LC50 = 1.0 % (newly hatched larvae), 0.5 % (unfed larvae) and unfed adults (1.6–3.2 %)	Abdel-Shafy and Zayed, 2002
A. indica A Juss (Meliaceae)	Neem oil and azadirachtin essential oil formulation	H. dromedarii	Significant effect on larva feeding, molting of nymph and molt ability at 2.5 μg/mL azadirachtin; Against adult contact LC50 is > 40.7 μg cm−2 and against larvae dipping LC50 = 5.0 μg/mL	Al-Rajhy et al., 2003
Calotropis procera (Asclepiadaceae)	A cardiac glycosidal (cardenolide) extract	H. dromedarii	Against larvae contact LC50 = 9.63 μg/cm2 and dipping LC50 = 1.096 μg/mL	Al-Rajhy et al., 2003
Cymbopogon winterianus	Ethanolic extracts of leaves	H. anatolicum	Against larvae LC50 (leaves extracts) = 0.14 %	Singh et al., 2014
Digitalis purpurea L. (Scrophulariaceae)	A cardiac glycosidal (digitoxin) extract	H. dromedarii	Against larvae contact LC50 = 4.08 μg/cm2 and dipping LC50 = 0.410 μg/mL.	Al-Rajhy et al., 2003
Eucalyptus camaldulensis Dehnh (river red gum)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibition of reproduction of female at 6.250 μl/ml; Against larvae LC50 = 0.207 μl/ml, LC90 = 1.653 μl/ml and LC95 = 2.978 μl/ml)	Djebir et al. (2019)
E. globulus Labill (blue gum)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibition of the reproduction in female at 6.250 μl/ml; Against larvae LC50 = 0.155 μl/ml, LC90 = 2.387 μl/ml and LC95 = 5.183 μl/ml	Djebir et al. (2019)
E. globoidea	dichloromethane extract of plant	H. rufipes	Significant repellent effects against adults (30–40 % of extract up to 120 min)	Magano et al. (2011)
Euphorbia aegyptiaca (Euphorbiaceae)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 0.2595 μg/μl (DE), 1.511 μg/μl (EA), 0.763 μg/μl (hexane) and 0.6117 μg/μl (ethanol).	Abdel-Shafy et al. (2007)
Francoeuria crispa (Asteraceae)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 1.069 μg/μl (DE), 0.455 μg/μl (EA), 0.849 μg/μl (hexane) and 0.656 μg/μl (ethanol).	Abdel-Shafy et al. (2007)
Geranium macrorrhizum (Geraniaceae)	Essential oils through hydrodistillation of arial part	H. lusitanicum	Against larvae LC50 = 1.37 mg/ml and LC90 = 2.87 mg/mL	Navarro-Rocha et al., 2018
Guierase negalensis (Combrataceae)	Leaves, Petroleum ether PE) and ethanolic extracts (EE)	H. anatolicum	100% failure of egg hatching: both PE and EE at 15%; IC50 for inhibition of hatchability: PE = 1.71 % and EE = 0.508 %; LC50 and LC99 (against larvae): PE = 2.08 and 14.09 % and EE = 0.787 and 11.054 %; 100 % inhibition of egg-laying of female: PE and EE = 15 %	Osman et al. (2014)
Haplophyllum tuberculatum (Rutaceae)	Essential oils from aerial parts	H. dromedarii	Against larvae LC50 = 0.5 %	Abdel-Shafy et al. (2007)
Lavandula stoechas L. (lavender)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibition of reproduction at 3.125 μl/ml; Against larvae LC50 = 0.253 μl/ml, LC90 = 2.212 μl/ml, and LC95 = 4.092 μl/ml	Djebir et al. (2019)
Mesembryanthemus forsskale (Aizoaceae)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 0.611 μg/μl (DE), 1.646 μg/μl (EA), 0.294 μg/μl (hexane) and 0.380 μg/μl (ethanol).	Abdel-Shafy et al. (2007)
Nicotiana tabacum	Ethyl-acetate extract of plant	H. rufipes	Significant repellent effects on adult tick (40% v/w of extract for the first 40 min).	Magano et al. (2011)
Origanum floribundum Munby (oregano)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibition of reproduction at 3.125 μl/ml; Against larvae LC50 = 0.131 μl/ml, LC90 = 0.982 μl/ml, and LC95 = 1.740 μl/ml	Djebir et al. (2019)
Reaumuria hirtella (Tamaricaceae)	Diethyl ether (DE), ethyl acetate (EA), hexane, and ethanol extracts of aerial parts	H. dromedarii	Against larvae LC50 = 124.68 μg/μl (DE), 16.417 μg/μl (EA), 8.382 μg/μl (hexane) and 23676.62 μg/μl (ethanol).	Abdel-Shafy et al. (2007)
Rosmarinus officinalis L. (rosemary)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibition of reproduction at 0.781 μl/ml; Against larvae LC50 = 0.108 μl/ml, LC90 = 0.495 μl/ml, and LC95 = 0.761 μl/ml	Djebir et al. (2019)
SaturejathymbraL. (Lamiaceae)	Volatile essential oil collected from arial part of plant at flowering stage through hydrodistillation	H. marginatum	100 % adult tick mortality in 3 h at 40 μl/L	Cetin et al. (2010)
Senna italica subsp. arachoides (Fabaceae)	Ethyl acetate extract of root	H. rufipes	Against adult LC50 = 8.66 % (w/v) in 24 h and 3.59 % (w/v) in 48 h	Magano et al. (2008)
Tagetes minuta L. (Asteraceae)	Essential oil from aerial parts and flowers	H. rufipes	Repellent EC50 for male ticks = 0.072 mL/mL and for female = 0.070 mL/mL; Significant number of nymphs (60%) delayed in moulting	Nchu et al. (2012)
Thymus capitatus L. (thyme)	Essential oil from leaves and flowering tops through hydrodistillation	H. scupense	100 % inhibit the reproduction in femaleat 1.562 μl/ml; Against larvae LC50 = 0.058 μl/ml, LC90 = 0.358 μl/ml, and LC95 = 0.600 μl/ml	Djebir et al. (2019)
Vitex negundo	Ethanolic extracts of leaves and roots	H. anatolicum	Against larvae LC50 (root extract) = 1.27 % and (leaves extract) = 0.011 %	Singh et al. (2014)
Withania somnifera	Ethanolic extracts of leaves	H. anatolicum	Against larvae LC50 (ethanolic extracts) = 10.12 %	Singh et al. (2014)

Although there has been a considerable progress in the recent past in natural product development research, most of the findings were restricted to in-vitro studies. The effects of geographical and climatic variations on the chemical constituents within the same plant species and identification of activity-based marker compound for quality assurance are the two key important impediments in large scale development of a natural formulation for the management of ticks. In our recent multicentered studies we observed a very wide variation of 10–90% in antitick activity of the same plant extracts prepared from 177 accessions collected from 17 states of India. The variations in antitick activity has recently been attributed to the variation in key compounds present in the extracts (Ghosh unpublished data). One more hurdle is expensive toxicology testing for new products which may have limited intellectual property (IP) protection. Other challenges include the economical supply of plant product, biased perception regarding chemical acaricides vis-à-vis phyto-formulation, quality protection after exposing to sunlight.

4.5. Immunization of hosts

Acquired resistance in ticks is expressed as reduced engorgement weight, increased duration of feeding, decreased number and viability of ova, blockage of moulting and death of feeding ticks (Wikel, 1996). During 1979, Allen and Humphreys conducted a preliminary experiment of immunization of cattle and guinea pigs using extracts of the gut and internal organs of D. andersoni and recorded protective efficacy against homologous challenge infestations (Allen and Humphreys, 1979). Thereafter, several researchers started working on the development of an anti-tick vaccine. However, in most of the cases, R. microplus was used as model parasite and consequently, majority of publications are dealt with R. microplus alone and the subject has been reviewed time to time. On the other hand, limited information is available against the multi-host tick, H. anatolicum (Willadsen, 2004; de la Fuente et al., 2007; Parizi et al., 2012; Lew-Tabor and Rodriguez-Valle, 2016; de la Fuente, 2018; Manjunathachar et al., 2014).

Earlier, Gill et al. (1986) reported the involvement of salivary proteins of H. anatolicum in hypersensitivity reaction as an indicator of resistance against homologous challenge in rabbits. Subsequently, several workers reported comparatively higher adaptive immunity in laboratory animals than in natural hosts (Ribeiro, 1989). Momin et al. (1991) and Singh et al. (1991) reported significantly adverse effect on ticks fed on animals repeatedly infested with H. anatolicum and reconfirmed the earlier observations of Gill et al. (1986). Ghosh et al. (1998) immunized rabbits with extracts of larvae and nymphs and a significant reduction in the engorgement percentage, engorgement weight and egg masses in ticks fed on immunized animals compared to ticks fed on a control group of animals was recorded. A significant reduction of nymphs (91.3%) and adults (79.7%) fed on calves immunized with 39 kDa larval antigen (Ghosh et al., 1999) while, 84.2%, 61.4% and 58.7% rejection of larvae, nymphs and adults, respectively, in ticks fed on animals immunized with 39 kDa nymphal antigen (Sharma et al., 2001) was reported. Further, the protective efficacy of cocktails of three polypeptides of 100, 59.4 and 37 kDa isolated from larvae of H. anatolicum was assessed in calves and significant protection of 70.6 %, 54.5 % and 61.9 % against the homologous challenge of larvae, nymphs and adults, respectively, was recorded (Das et al., 2000). Subsequently, Das et al. (2003) used a mixture of 106.8 and 68 kDa antigens isolated from midgut extract of H. anatolicum and reported 74.4 % and 52.2 % decrease of nymphs and adults, respectively, after challenge infestations on cattle. In the same year, Singh and Ghosh (2003) isolated 34 and 29 kDa glycoprotein from unfed larvae of H. anatolicum and R. microplus, respectively, and reported the direct effect of immunization (DT %) of 69 % and 52 % against larvae and adults of H. anatolicum and 60 % against R. microplus adults. Hakim et al. (2011) evaluated three major glycoproteins (97, 66 and 40 kDa) purified from H. dromedarii adults and larvae and demonstrated 63–67 % reduction in egg hatchability of ticks fed on immunized animals in comparison to ticks fed on control animals.

Successively, transmission-blocking potentiality of antigens was studied viz., Das et al. (2005) used 37 kDa larval antigen of H. anatolicum and recorded reduced level of T. annulata infection in ticks fed on immunized calves compared to control groups. The results were substantiated through staining of salivary glands of challenged ticks, polymerase chain reaction (PCR) amplification of T. annulata specific 721 bp gene segment (30 kDa major merozoite surface antigen gene) and in vitro infectivity study on bovine mononuclear cells. Overall they concluded that a partial reduction in the growth rate of T. annulata in ticks is possible by immunization of hosts with 37 kDa larval antigen.

Though a lot of work has been done with native antigens but most significant results were obtained after the discovery of Bm86 molecules from R. microplus and development and commercialization of Bm86-based vaccines as TickGARD/Gavac against R. microplus infestations on cattle (Willadsen et al., 1989; de la Fuente et al., 2007). On the similar line, protective efficacy of homologue of Bm86 gene in Hyalomma species was studied. For example; de Vos et al. (2001) identified a homologue of Bm86 in H. anatolicum and reported 50 % protection against H. anatolicum by limited immunization trial. Subsequently, Ebrahimi et al. (2012) successfully established the presence of cross-reactive epitopes between Bm86 and HAO3 antigens of H. anatolicum. Said et al. (2012a) cloned and characterized the Hd86 antigen from H. scupense, an ortholog of the Bm86 gene and reported very low intra-specific diversity in amino acid sequences of Hd86 of different isolates of H. scupense of Tunisia and a 59.1 % protection against the nymphal stage of H. scupense and no protection against adults was reported (Galai et al., 2012). To explain the variation in results, Said et al. (2013) determined the expression profile of Hd86 in different stages and demonstrated a significant reduction (p < 0.001) in the number of transcripts level during the feeding period and particularly after moulting to adults (12.78 and 9.25 fold in unfed males and unfed females) respectively. Lower Hd86 mRNA levels in adult ticks may result in lower protein levels in immunized animals. Concurrently, Said et al. (2012b) studied Bm86 ortholog in four different Hyalomma species, viz., H. marginatum (Hm86), H. excavatum (He86), H. dromedarii (Hdr86) and H. scupense (Hd86-A1) and suggested that Hd86-A1 vaccine candidate might be more appropriate to target Hyalomma tick species in contrast to Bm86 commercial vaccines. Kopp et al. (2010) raised series of monoclonal antibodies against synthetic peptides of BD86, a Bm86 homologue of R. decoloratus and detected strong signal of one of the antibodies (mAbs 12.1) in immunohistochemical analyses with the gut of four species of ticks including H. anatolicum. But no further progress was reported to exploit the observation. Further, Haa86, a Bm86 homologue of H. anatolicum was generated and tested against homologous challenge infestations. The protective efficacy was variable from 47- 60% against larvae and 40–80% against adults (Azhahianambi et al., 2009a, 2009b; Jeyabal et al., 2010; Kumar et al., 2012a). Recently five antigens namely; Subolesin (SUB), Calreticulin (CRT), Cathepsin-L like cysteine protease (CathL), Ferritin 2 (FER2) and Tropomyosin (TPM) ortholog of H. anatolicum were selected based on their established role in tick physiology and metabolism in different tick species. A very low level of variation of 0.6–2.4 %, 0.3–1.8 %, 0.3 to 6.4, 0.1–0.6% and 0.1–1.3 % in the deduced amino acid sequences of various field isolates of H. anatolicum was observed in SUB, CRT, CathL, FER2 and TPM genes, respectively. Similarly, the amino acid sequence identity for the same genes in other ticks species was 77.4–99.3 %, 85.1–99.7 %, 57.5–89.5 %, 80.1–90.9 % and 98.8–99.9 % against reference H. anatolicum IVRI II strain (Kumar et al., 2017; Manjunathachar et al., 2019).

Following transcriptomic analysis of SUB, CRT, CathL, FER2 and TPM genes revealed that amongst all the life stages except in eggs and frustrated females, the differences in fold change in expression (FCE) of SUB gene was not significant (p > 0.05). In eggs and in frustrated females (tick released on animal but not allowed them to feed for 24 h), relative expression of SUB gene was significantly (p < 0.05) higher than in engorged larvae, nymphs, females and in unfed males. The differences in FCE of CRT gene were not significant (p > 0.05) in all the life stages except in fed males and in between engorged larvae and females. The FCE of CathL gene was (p < 0.001) highest in frustrated females followed by unfed females than in all other stages while differences in FCE were not significant (p > 0.05) among all the other stages except in between eggs and larvae. Similarly, in FER2, only statistically significant (p < 0.01) low FCE was recorded in eggs. Unlike FER2, the FCE of TPM gene was significantly (p < 0.001) higher in fed larvae, nymphs, females, males and in the unfed adult stage (P < 0.01) (Kumar et al., 2017; Manjunathachar et al., 2019). The functional properties of the genes were studied by RNA interference (RNAi) technology and following immunization of animals with recombinant proteins, SUB, TPM, FER2, CRT and CathL, 65.4%, 63.7%, 51.7 %, 41.3% and 30.2%, respectively, protection against larvae was observed. However, against adults, the TPM and FER2 proteins were more effective (Kumar et al., 2017; Manjunathachar et al., 2019). The results of different immunization studies clearly indicated that the majority of the experiments were conducted using the homologous challenge system and the protective efficacy of the antigens was variable. Further, it is emphasized that a multi-antigenic vaccine involving multi-targets is the suitable option for getting significant cross-protection against heterologous challenge (Schetters and Jansen, 2015, PCT/EP2014/056248).

In an attempt to develop cross-protective vaccine, Rodriguez-Valle et al. (2012) immunized cattle and camels with rBm86-based vaccine and challenged with H. dromedarii and A. cajennense ticks and recorded partial efficacy against former tick and no effect against later tick species. Similarly, cross-protective efficacy of Gavac™ was assessed against H. anatolicum, Indian isolate and 25 % efficacy was recorded (Kumar et al., 2012b). The cross-protective efficacy of rHaa86, SUB, CRT and CathL was also tested against R. microplus but the results were not much encouraging and revealed that the species-specific vaccine is more efficacious (Kumar et al., 2017). Ideally, a cross-protective anti-tick vaccine is an appropriate strategy towards simultaneous control of multi-tick species but for region-specific management of the vector of animal and human pathogens, a vaccine against H. anatolicum has a distinct position in tropical and sub-tropical countries including India.

5. Integrated control strategies

As an alternative to acaricides, a number of methods including the maintenance of hosts naturally resistant to ticks, pheromone-impregnated decoys for attracting and killing ticks, biological control using natural enemies, resistance monitoring and strategic application of effective acaricides, natural anti-tick formulation and vaccines are in use (Hanifah et al., 2011; Silva et al., 2009; Madzimure et al., 2011; Merino et al., 2011; Willadsen, 2006; de la Fuente and Kocan, 2006; Ghosh and Nagar, 2014; Kumar et al., 2020). Vaccine-controlled field trials in combination with acaricide treatment demonstrated that an integrated approach resulted in significant management of tick infestations while reducing the use of acaricides (de la Fuente et al., 2007; de la Fuente and Kocan, 2003). These trials proved that management of ticks by vaccination has an added advantage in terms of cost-effectiveness, safety and for preventing the selection of drug-resistant ticks (de la Fuente et al., 2007; Rodriguez-Valle et al., 2004). Cost-effective analysis of the vaccine in the integrated tick management system revealed a 60% reduction in the number of acaricidal treatments, increased milk production capabilities and a preventive effect on the transmission of babesiosis in vaccinated herds resulted in savings of US$ 23.4 /animal/year (de la Fuente et al., 1998). At present, there is no vaccine available against Hyalomma tick and dependency on acaricides is increasing. Henceforth, to reduce the dependency on acaricides and management of ticks in a sustainable manner following strategies can be taken:

• 1.Regular monitoring of resistance using bioassay, biochemical and molecular assays.
• 2.Formulation of region-specific tick management strategies on the basis of resistance data.
• 3.Use of characterized phytoformulations;
• 4.Rearing of local poultry birds, voracious feeder of tick stages, along with animals;
• 5.Pasture spelling/burning, wherever possible;
• 6.Prevention of invasion of wild animals into pasture areas.

Though, implementation and monitoring of ITM is a difficult task in most of the countries. It is necessary to implement ITM at the policy level regions/sector-wise and in a phased manner to increase the level of acceptability of the technology at farmer level.

6. Future prospects

Literature reveals the acaricide resistant status in Hyalomma species is comparatively less in comparison to R. microplus and most of the SP and amidine compounds are still working against the species. This is because of the multi-host life cycle of the vector and exposure to different chemicals is comparatively less in comparison to one host tick. However, since co-infestation is the common features in many tropical and sub-tropical countries, the species will definitely develop resistance against a wide range of chemicals in the coming years. A vaccine against H. anatolicum can be an effective sustainable measure along with strategic use of natural formulations. Significant lead has been reported but due to severe shortage of funding opportunities in tick vaccine research globally, the work is not progressing in ladder manner. There is an urgent need to increase funding support for research on one health concept in which vaccine against Hyalomma spp. forms a focused area of research. The different groups working on tick vaccine globally should come together in a consortium mode to develop suitable immunoprophylactic measures to mitigate the burning problem of ticks and tick-borne diseases.

Declarations

Author contribution statement

All authors listed have significantly contributed to the development and the writing of this article.

Funding statement

This work was supported by the Indian Council of Agricultural Research, New Delhi through National Agricultural Science Fund [Grant number NASF/ABA-6015/2016-17/357 and NFBSFARA/BSA-4004/2013-14].

Data availability statement

Data included in article/supplementary material/referenced in article.

Declaration of interests statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.