Hyalomma asiaticum - an overview (2023)

8.1.3.9 Tamdy Virus

Taxonomy. Three strains of TAMV isolated in Uzbekistan (LEIV-1308Uz), Armenia (LEIV-6158Ar), and Azerbaijan (LEIV-10226Az) were completely sequenced.²⁰ Phylogenetic analysis of the full-length sequences showed that TAMV is a novel member of the Nairovirus genus, forming a distinct phylogenetic lineage (Figures 8.10–8.12). The similarity of the amino acid sequence of TAMV RdRp (L-segment) with those of other nairoviruses is 40% aa, on average. The similarity of the RdRp of TAMV with that of the nairoviruses associated predominantly with ixodid ticks (CCHFV, Hazara virus (HAZV), and DUGV) is higher (40% aa) than that with viruses associated with argasid ticks (ISKV and CASV) (38% aa). The similarity of the TAMV polyprotein precursor of Cn and Gc with that of other nairoviruses is less than 25% aa. The similarity of the amino acid sequence of the nucleocapsid protein (S-segment) of TAMV is 33% aa with ixodid nairoviruses and 28% aa with argasid nairoviruses. Phylogenetic analysis of the catalytic core domain of the RdRp of the nairoviruses confirms that TAMV forms a novel group in the Nairovirus genus (Figures 8.10–8.12).²⁰

Genetic diversity among the three sequenced strains of TAMV is low. The prototypic strain LEIV-1308Uz, isolated in central Asia, has 99% nt identity in the L-segment with LEIV-10226Az from Transcaucasia. The L-segment of the strain LEIV-6158Ar has 94.2% nt and 96.3% aa identity with the L-segment of LEIV-1308Uz. The similarity of the M-segment of LEIV-1308Uz with those of LEIV-10226Az and LEIV-6158Ar is 93% nt and 89% aa, respectively. The similarity of the S-segment among the three strains is 93–95% nt.²⁰

Arthropod Vectors. H. asiaticum ticks are apparently a main reservoir of TAMV. More than half (57%) of TAMV isolations were obtained from H. asiaticum asiaticum ticks, 6% from H. asiaticum, 8% from H. anatolicum, 6% from H. marginatum, 6% from Rhipicephalus turanicus, and 2% from Haemaphysalis concinna. The infection rates of male and female ticks in endemic territory were 1:210 and 1:200, respectively. The infection rate of H. asiaticum nymphs was 20 times lower.^7,10,14,16 Furthermore, TAMV was isolated from larvae of H. asiaticum, which were hatched from eggs in the laboratory, indicating transovarial transmission of the virus. H. asiaticum asiaticum ticks are the most xerophilous subspecies of the Hyalomma genus (Ixodinae subfamily),²¹ a characteristic that allows TAMV to be distributed over the Karakum desert in Turkmenistan, the Moinkum desert in Kazakhstan, and the central part of the Kyzyl Kum desert in Kazakhstan and Uzbekistan.⁷.

Animal Hosts. The larvae of H. asiaticum feed on ruminants, hoofed animals, small predators, hedgehogs, birds, and reptilians. One of the major hosts of H. asiaticum preimagoes is the great gerbil (Rhombomys opimus). Wild animals, as well as sheep and camels, are the hosts for H. asiaticum imagoes and may be involved in the circulation of TAMV (Table 8.13).

Human Pathology. Sporadic cases of the disease associated with TAMV was registered in Kyrgyzstan in October 1973, when TAMV was isolated from the blood of a patient with fever (39°C), headache, arthralgia, and weakness.¹⁶ H. asiaticum asiaticum ticks rarely attack humans, and no outbreaks of TAMV fever have been registered; however, human infection by H. asiaticum ticks is still possible through contact with livestock necessitated by economic activities (e.g., sheep shearing).

Mononegavirales: Rhabdoviridae and Nyamiviridae (ssRNA-)

The viral order Mononegavirales was established in 1991 by ICTV to accommodate related viruses (assigned in three families, Filoviridae, Paramyxoviridae, and Rhabdoviridae) with nonsegmented, linear, single-stranded negative-sense RNA genomes. Another two families Bornaviridae and Nyamiviridae joined the other three mononegavirales families in 1996 and 2014, respectively. In 2016, the order Mononegavirales was edited by including of two new families, Mymonaviridae and Sunviridae, and upgrading of subfamily Pneumovirinae (Paramyxoviridae) to family status Pneumoviridae (Afonso etal., 2016).

In 2013, by the proposals of Kuhn etal. (2013) and Mihindukulasuriya etal. (2009), the new family Nyamiviridae (ssRNA-), created in the order Mononegavirales (Table 10.5), comprises the genus Nyavirus including two TBVs, Nyamanini nyavirus (NYMV) and Midway nyavirus (MIDWV). NYMV was discovered in 1957 and repeatedly isolated from land birds and Argas spp. ticks. It is endemic in South Africa, Egypt, Thailand, Nigeria, Nepal, and Sri Lanka. MIDWV was discovered in 1966 and repeatedly isolated from seabirds and Ornithodoros spp. ticks. It is endemic in Hawaii, United States, and Japan. NYMV and MIDWV are serologically related but clearly distinct from each other and not related serologically to any other virus tested (rev. in Kuhn etal., 2013). In 2014, Tesh etal. proposed a new virus species in this family, Sierra Nevada nyavirus (SNVV). Based on its genomic structure and phylogeny, Sierra Nevada virus is closely related to NYMV and MIDWV, indicating that it is a third member of the Nyavirus genus (Rogers etal., 2014). SNVV was originally isolated at the University of California, from Vero cell cultures inoculated with a homogenate of Ornithodoros coriaceus ticks collected in Northern California. The virus caused a viral cytopathic effect in both Vero and Baby Hamster Kidney cells within 48h after inoculation, and intracranial inoculation of newborn mice with SNVV leads to disease and death within 2–3days (Tesh etal., 2014).

By virome analysis of I. scapularis, Tokarz etal. (2014b) identified a new mononegavirales-like virus with the greatest similarity to the Nyamanini and Midway viruses (17% amino acid identity).

Molecular properties

Phylogenetic analyses of the S segment coding for the nucleocapsid (N) protein suggest the existence of at least three genetic subgroups, although there is a proportionally greater sequence diversity in the M RNA segment. It is difficult to correlate such variation with the geographical distribution of the virus, however, due to the random movement of livestock and the international trade in animals that may either harbour infection or be carrying infected ticks (Rodriguez et al., 1997). Different tick hosts may also drive sequence variability, particularly in the envelope glycoproteins. For example, Hyalomma asiaticum is the principal host in China as opposed to say, H. marginatum in West Africa (Camicas et al., 1994, Yen et al., 1985). Bird migration over long distances may also confound any attempt at locating point source of outbreaks, especially by use of molecular sequencing methods.

A recent study of Chinese isolates collected over a prolonged period from 1966 to 1988 from the Xinjiang Autonomous Region in western China illustrates well these difficulties of interpretation. Sequencing has clearly shown that virus within an epidemic may originate from a variety of sources (Morikawa et al., 2002). This study examined the M RNA segment coding for viral glycoproteins: several isolates were found to cluster with a variant previously isolated in Nigeria. Using highly conserved primers specific for the polymerase gene of the L RNA segment, Honig and associates have reported that the Nairovirus genus is highly divergent. Moreover, Honig et al. (2004b) showed a clear phylogenetic lineage for those nairoviruses spread by hard ticks. Thus, Crimean-Congo haemorrhagic fever virus along with other closely related members of the Nairovirus genus has evolved closely with their tick hosts.

Examining seven isolates from China, Morikawa et al. (2002) reported that the ORF encoded by the M RNA segment contains a hypervariable region at the N-terminus spanning the first 250 amino acid residues. The location of the N-terminus of Gn within the ORF is still not certain, but Morikawa and colleagues have predicted its location either at residue 1046 or at residue 1054, with some variation between isolates. This locates the cleavage some 50 amino acids downstream of the nearest hydrophobic region towards the end of Gn, similar to that found in the Nairovirus Dugbe. The implication of this is the existence of a common coding strategy for all genes expressed by the M RNA segment, with a non-structural protein located at the N-terminus of the ORF, followed by Gn and Gc, respectively.

The Crimean-Congo haemorrhagic fever L RNA segment codes principally for the viral RNA polymerase. This segment, at 12,164 nucleotides, is almost twice the length of, e.g. that of Rift Valley fever, coding for an L protein of 3944 amino acids as compared to 2149 resides for the L protein of Rift Valley fever virus (Honig et al., 2004a; Kinsella et al., 2004). The increase in size is accounted for by an extension at the N-terminus, this coding for an ovarian tumor (OTU)-like protease. This may have a role in autoproteolysis of this large protein or have a role in its processing through the ubiquination pathway. Other functions are almost certainly represented in this N-terminus sequence, the nature of which is as yet unclear.

7.2.1.5 Wad Medani Virus

History. The Wad Medani virus (WMV) was originally isolated by R.M. Taylor and colleagues from Rhipicephalus sanguineus (family Ixodidae, subfamily Rhipicephalinae) ticks, collected from sheep near Wad Medani village (Sudan, Africa) in November 1952. On the basis of its serological properties, WMV was assigned to the Kemerovo antigenic group (family Reoviridae, genus Orbivirus).^1,2 Later, more than 20 strains of WMV were isolated from other species of ticks: Hyalomma asiaticum (Central Asia); H. anatolicum (Iran, Pakistan); H. marginatum (India); Amblyomma cajennense (Jamaica); Rh. Microplus, formerly Boophilus microplus) (Malaysia); and Rh. guilhoni and Rh. evertsi (family Ixodidae, subfamily Rhipicephalinae) (both species found in Sudan, Egypt, Senegal, India, Pakistan, Iran, and Jamaica).^1,3

Taxonomy. The genome of the orbiviruses has 10 segments of dsRNA, which encode seven structural (VP1–VP7) and four nonstructural (NS1–NS4) proteins.⁴ Scientists have sequenced the genome of strain LEIV-8066Tur (GenBank ID, KJ425426–35), isolated from H. asiaticum ticks in Baharly district, Turkmenistan. The most conservative protein of the orbiviruses is an RdRp (Pol, VP1). A comparison of full-length VP1 amino acid sequences of WMV with those of other tick-borne orbiviruses revealed a 54% identity. A phylogenetic analysis based on a comparison of full-length VP1 (Pol), VP3 (T2), and VP7 (T13) amino acid sequences of the orbiviruses is presented in Figure 7.1. The major antigenic determinants of orbiviruses are located on three proteins of the outer and inner layers of the capsid. The most divergent are VP2 and VP5 proteins. The VP2 protein forms the outer layer of the capsid and carries the main neutralizing and receptor-binding sites. In addition, the VP2 protein is one of the virulence factors of the orbiviruses. The similarity of the VP2 amino acid sequences of WMV with those of other tick-borne arboviruses is 26–30%. The similarity of the VP5 protein of WMV with that of other tick-borne orbiviruses is 45%, on average. Among the structural proteins, the most conservative one is VP3 (T2), which forms the inner layer of the capsid. The VP7 protein (T13) is involved in the virus–cell interaction and, like the VP2 protein, is one of the virulence factors, defining, in particular, the infectivity of the virion. In an intact virion, the antigenic epitopes VP7 (T13) are hidden and therefore cannot be blocked by neutralizing antibodies. VP7 (T13) has group- and species-specific antigenic determinants. The similarity of the VP7 (T13) amino acid sequences of WMV to those of mosquito-borne orbiviruses is 46%, and to those of tick-borne viruses is 67%.

Genomic segment 9 of the orbiviruses encodes the viral enzyme VP6 (Hel), which possesses an RNA-binding and helicase activity. The similarity of VP6 (Hel) of WMV with that of other tick-borne orbiviruses is in the range 36–38%. It has been shown that segment 9 of GIV, BAKV, and BTV has an additional ORF that encodes a protein denoted VP6a or NS4 with an unknown function. Like other tick-borne orbiviruses, WMV also encodes VP6a ORF. Noted that, although the amino acid sequences VP6a of GIV, BAKV, and WMV have a low level of similarity (20–30%), they are the same size (195 aa) and have two closed start codons. The length of VP6a ORF in tick-borne arboviruses is almost two times larger than that of BTV.⁵ The phylogenetic analysis shown in Figure 7.1, an analysis based on a comparison of structural and nonstructural proteins of the orbiviruses, reveals that the topology of WMV on the tree confirms the classification of the virus into antigenic group B of the genus Orbivirus.

Epizootiology. Antibodies against WMV have been found in camels and buffaloes.¹ Two strains of Seletar virus, which is closely related to WMV, were isolated by A. Rudnik from B. microplus ticks, collected in the Seletar area of Singapore in January 1961. Because B. microplus is a one-host tick, spending its entire life span on a single host, transovarial transmission would seem to be necessary for preservation of the viral population.^5,6 Fourteen strains of WMV were isolated during virological monitoring of different ecosystems in Northern Eurasia: 10 strains in Turkmenistan,^7–11 2 in Kazakhstan,^12–16 1 in Tajikistan, and 1 in Armenia.^17–19

In Turkmenistan, all of the strains of WMV were isolated from H. asiaticum ticks, collected from sheep and camels in either Ýolöten district of Mary province (in semiarid landscapes) or in Baharly district of Ahal province (in arid landscapes) in 1972, 1973, and 1981.^7–10 In Kazakhstan, two strains were isolated from H. asiaticum in arid landscapes of Balkhash district (Almaty province) in 1977. The proportion of infected ixodids has been estimated as 0.094%.^12–16 In Tajikistan, one strain of WMV was isolated from H. anatolicum ticks. These ticks made up 76.5% of all ixodids in this territory, and the proportion of infected H. anatolicum ticks reached 0.002%.^17,19 In the arid climate of the southern part of Tajikistan, one or two generations of ixodid ticks can develop during the year. WMV was isolated from hungry, overwintered imagoes that exhibited transstadial transmission of the virus.^13,17 Experimental infection of calves has shown that the level of WMV viremia is sufficient to infect H. anatolicum larvae, which subsequently transferred the virus to imagoes that provides activity and stability for the natural foci of WMV.²⁰ Immunity to WMV among the human population in southern Tajikistan reaches 7.8–10.3%, while in the northern provinces it does not exceed 2.1%.^20,21 In Transcaucasia, WNV was isolated from H. asiaticum ticks collected near Nakhichevan, Azerbaijan, in 1985.¹⁸ The results obtained from the isolation of WMV in Kazakhstan, Central Asia, and Transcaucasia indicate that H. asiaticum and H. anatolicum ticks play the main role in maintaining natural foci of the virus in pasture biocenoses and in arid and semiarid landscapes.

Epidemiology. There is no indication that WMV is pathogenic to humans.

1 Introduction

Ticks are arthropods that parasitize several animal classes and present blood feeding behavior in most developmental stages (Mans,2014; Dantas-Torresetal., 2019). These parasites are distributed worldwide and are the vectors of pathogens to animals and humans. An infected tick feeding on a non-infected host can lead to the transmission of pathogens that are harmful to the host health (UnitedStates Department of Health and Human Services,2020; Dantas-Torresetal,2012; Perveen,etal., 2021; TBDWG,2018). Tick-borne diseases include mainly anaplasmosis, babesiosis, and theileriosis in animals, and spotted fever, ehrlichiosis, anaplasmosis, Powassan virus disease and Lyme disease/ borreliosis in humans (Perveen,etal., 2021; Sonenshineand Roe,2014; Lew-Taborand Rodriguez Valle,2016).

Ixodidae is a family of hard ticks occurring in temperate, subtropical, and tropical regions (Apanaskevichand Oliver,2014). Ixodes, Haemaphysalis, Hyalomma, Amblyomma and Rhipicephalus are the Ixodidae genera of most importance worldwide regarding transmission of pathogens that cause human or veterinary diseases (Boulangeretal., 2019; TBDWG,2018).

Ixodes ricinus, Ixodes scapularis, Ixodes persulcatus and Ixodes pacificus are the main vectors of Borrelia burgdorferi genospecies, the agents of Lyme disease/borreliosis, which is critical to human health being the most common tick-borne disease, especially in the US (UnitedStates Department of Health and Human Services,2020; Mead,2015; Steereetal., 2004; TBDWG,2018). Another ixodid tick of medical importance is Ixodes holocyclus, endemic in Australia, which causes toxicosis inducing paralysis in humans and several animal species, including birds, dogs, cats, among others (Barkerand Walker,2014; Hall-Mendelinetal., 2011; Raghavanetal., 2021).

Haemaphysalis longicornis is native from Eastern Asia and invasive in Australia, New Zealand, and recently in the United States, in part due to its ability to parasitize different hosts (UnitedStates Department of Health and Human Services,2020; TBDWG,2018). This tick species is the main vector of Theileria protozoa in Asia (Heath,2016; Irvin,1987; Tuftsetal., 2019). Theileria sergenti is transmitted to domestic livestock and can lead to death, being responsible for major economic losses in Asian countries (Liu,etal., 2010; Songand Sang,2003; Tanakaetal., 1993). Also in Asia, mainly in China, Hyalomma asiaticum ticks are important vector of pathogens, among them Crimean–Congo hemorrhagic fever virus and the agent of Q-fever, Coxiella burnetii (Apanaskevichand Horak,2010; Chenetal., 2010; Duronetal., 2015; Jiaetal., 2022; Wuetal., 2013).

The lone star tick, Amblyomma americanum, can parasitize a variety of animals, being one of the most aggressive vector of pathogens and an important tick species that affects public health and the economy in the United States (UnitedStates Department of Health and Human Services,2020; Goddardand Varela-Stokes,2009; Levinetal., 2017; TBDWG,2018). All motile stages can feed on humans and spread Rickettsia rickettsii (Maver,1911). Recently, several studies have also associated red meat allergy to galactose-α-1,3-galactose (alpha-gal sugar) inoculated during A. americanum tick bite (Comminsetal., 2011; Comminsand Platts-Mills,2013; Crispelletal., 2019; Macdougalletal.,2022; Mitchelletal., 2020; Sharmaetal., 2021; vanNunen,2015; TBDWG,2018). In the Caribbean, Central and South America, other species of the genus Amblyomma play roles in the transmission of pathogenic Ehrlichia sp. (Amblyomma variegatum) and Rickettsia spp. (Amblyomma cajennense sensu lato., Amblyomma mixtum, Amblyomma sculptum, and Amblyomma ovale) (Camusand Barre,1995; Estrada-Peñaetal,2019; Navaetal., 2014).

The brown dog tick, Rhipicephalus sanguineus s.l., is widely distributed in the world and parasitize humans and animals. This tick species complex is responsible for transmitting multiple pathogens, such as Babesia protozoa, and also the bacteria Ehrlichia and Rickettsia (Dantas-Torres,2008; Dantas-Torresetal., 2006; Estrada-Peñaand Jongejan,1999; Jongejanand Uilenberg,2004). The cattle tick species, Rhipicephalus microplus, Rhipicephalus annulatus and Rhipicephalus australis, are of great economic importance in the world, given its widespread distribution across cattle-producing areas in the tropics and subtropics, and the transmission of Babesia bovis, Babesia bigemina and Anaplasma marginale (Alietal., 2016). Cattle tick parasitism leads to host anemia and consequently decrease in meat and milk production, representing one of the main causes of losses in livestock industry (Jongejanand Uilenberg,2004; Jonsson,2006; Perveen,etal., 2021). Annual economic losses caused by R. microplus infestation reach US$ 3.2 billion in Brazil alone (Grisietal., 2014).

These different tick species are responsible for the major ixodid tick-borne diseases reported worldwide and their increased abundance and range expansion could be related to many factors, including climatic, ecological and anthropological changes (Medlocketal., 2013). Currently, it is known that the interaction of humans, domestic and wild animals,and vectors is essential to pathogen transmission (Sprongetal., 2018).

Treatment of animal hosts with synthetic chemical pesticides (acaricides) has been the major approach to reduce tick infestations and prevent the transmission of tick-borne pathogens. There are seven chemical classes marketed worldwide for tick control in domestic animals, namely: organophosphates, synthetic pyrethroids, macrocyclic lactones, formamidines, benzoylphenyl ureas, phenylpyrazoles and isoxazolines (Gasseletal., 2014; Recketal., 2014; Rufeneretal., 2017). However, the use of these chemical compounds over the years led to the selection of tick populations resistant to most of these drugs (Jongejanand Uilenberg,2004). Interestingly, R. microplus is the tick species with the highest number of reports of resistance worldwide, having developed resistance to all major acaricide classes marketed for its control (Dzemoetal., 2022; Rodriguez-Vivasetal., 2018; Vilelaetal., 2020). Also, field populations with broad resistance to acaricides have been described in Brazil (Klafkeetal., 2017; Recketal., 2014).

Currently, a central concern regarding tick control methods is identifying strategies that are both effective and environmentally friendly (dela Fuente etal., 2007). In this context, biological control (biocontrol) methods have been explored (Samishetal., 2004). The introduction of a competitive species in the same habitat of pest species is a classical control method. However, this tool has disadvantages when both species are non-native to the affected area, or if the predator attacks non-target species (Ostfeldetal., 2006; Stiling,2004). Therefore, it is important to perform pre-release risk assessment (Reinbacheretal., 2021; Simberloff,2012). Entomopathogenic fungi, like Metarhizium brunneum (formerly Metarhizium anisopliae), have proven an effective alternative to reduce I. scapularis population, while also indicating to be a safe approach, since it does not affect non-target arthropods communities that may be present at the application site. On the other hand, more than one application is needed to obtain positive results (Bharadwajand Stafford,2010; Fischhoffetal., 2017). Application of M. brunneum in association with acaricides has been shown to increase effectiveness of the treatment in the control of resistant R. microplus strains (Websteretal., 2015), suggesting biocontrol methods in combination with other strategies as an alternative to control tick infestations (Beys-da-Silvaetal., 2020).

A sustainable, eco-friendly and economically favorable approach to tick control is the use of vaccines (dela Fuente etal., 2007, 2017; Guerreroetal., 2012b). Therefore, many efforts have been made to develop an efficient vaccine that confer protection against different tick populations (Guerreroetal., 2012b; Parizietal., 2012). Based on recombinant Bm86 (midgut glycoprotein antigen), two vaccines were developed against R. microplus from Australia and Cuba (TickGARD and GAVAC, respectively) (Canalesetal., 1997; Willadsenetal., 1995). TickGARD vaccine is not currently available for use, while GAVAC it is still commercialized. However, both vaccines failed to show efficiency worldwide (Guerreroetal., 2012b). On the other hand, different studies have shown that Bm86 and its homologues induce protection against R. annulatus (Fragosoetal., 1998), R. australis (Hüeetal., 2017) and Rhipicephalus decoloratus (Odongoetal., 2007), which can be very useful due to eventual coexistence of R. microplus and other tick species across the same area (Parizietal., 2012). Nevertheless, to date, no effective vaccine against R. microplus and other ticks has been brought forward. Thus, the control of tick parasitism and tick-borne diseases in humans and animals is still dependent on acaricide treatment. Serious limitations associated with the application of acaricides have intensified the search for novel tick control methods (Rodriguez-Vivasetal., 2018).