Int J Pharm Pharm Sci, Vol 14, Issue 8, 1-15Review Article

TICK-BORNE ZOONOTIC DISEASES AND ITS CONTROL

NIDHI YADAV, RAVI KANT UPADHYAY^*

Department of Zoology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur
^*Email: rkupadhya@yahoo.com

Received: 15 Feb 2022, Revised and Accepted: 08 Jun 2022

ABSTRACT

The present review article explains different zoonotic diseases transmitted by various species of ticks. This article emphasizes various animal hosts, transmission and prevalence of various zoonotic diseases caused by a virus, bacteria, protozoans in different eco-climatic regions of the world. This article also explains various diagnostic methods applied for the detection of disease pathogens, treatment methods and prophylactic measures. It recommends tick saliva antigen-based oral vaccines and antibiotics as treatment methods. It also suggests use of various bait formulations and cultural control methods for deterring ticks from blood feeding. This article signifies the need of pesticides for control of ticks and tick-borne diseases.

Keywords: Ticks, Zoonotic diseases, Pathogens, Control methods, Biopesticides, Powassan encephalitis

© 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
DOI: https://dx.doi.org/10.22159/ijpps.2022v14i8.44449. Journal homepage: https://innovareacademics.in/journals/index.php/ijpps.

INTRODUCTION

Ticks are implicated in the transmission of a number of infectious diseases caused by various groups of pathogens such as bacteria, viruses, and protozoa. Ticks spread infectious diseases such as Lyme borreliosis, ehrlichiosis, anaplasmosis and babesiosis. In the last four decades due to the movement of human population, domestic and wild animals, trade and traffic ticks are arriving into new endemic regions of the world. Exposure of tick-borne pathogens is increasing in geographic ranges that are resulting in heavy morbidity and mortality. Ticks-borne disease severely affecting human health and are more dangerous than envenomation [1]. Few tick species such as Hyalomma and Ixodes ricinus, Ixodes scapularis, Amblyomma americanum, Dermacentor variabilis infect large number of vertebrate hosts, including migratory birds. Many of these are responsible for the spread of spotted fever caused by Rickettsia species [2] (table 1). Borrelia burgdorferi infection is common in horses, while Borrelia miyamotoi in humans [3]. There is an alarming situation as few TBDs such as Lyme disease is, expanding endemic areas of the new geographic range due to increased anthropogenic activities, migration of birds and animal trade [3].

Source of information

For writing this comprehensive research review on tick-borne diseases, various databases were searched. For the collection of relevant information specific terms such as medical subject headings (MeSH) and key text words, such as “disease pathogens”, “transmission by ticks” published till 2022 were used in MEDLINE. Most especially for retrieving all articles pertaining to the use of tick-borne diseases and its control, electronic bibliographic databases was searched and abstracts of published studies with relevant information on the tick-borne diseases were collected. Furthermore, additional references were included through searching the references cited by the studies done on the present topic. Relevant terms were used individually and in combination to ensure an extensive literature search. For updating the information about a subject and incorporation of recent knowledge, relevant research articles, books, conferences proceedings and public health organization survey reports were selected and collated based on the broader objective of the review. This was achieved by searching databases, including SCOPUS, Web of Science, and EMBASE, Pubmed, PMC, Publon, Swissprot, Google searches” From this common methodology, discoveries and findings were identified and summarized in this final review.

Tick hosts and transmission

Ticks are currently considered to be second only to mosquitoes as vectors of human infectious diseases in the world. Ticks are highly active small-sized vectors which parasites pets like dogs and cats and spread series of zoonotic diseases. There is a range of vertebrate hosts such as sheep, cows and horses [4] and several ungulate species which are used by ticks feeding and propagation hosts. Free-living ungulates are hosts of ixodid ticks and reservoirs of tick-borne microorganisms in central Europe and many regions around the world [5]. Ungulates are amplifying and dilution hosts, of two important pathogens Anaplasma phagocytophilum and Borrelia burgdorferi [6] (table 1). The incidence of zoonotic diseases is massively increased due to the presence of various hosts and suitable environmental conditions. All these factors help in establishment of tick population as large number of animal hosts are easily available and ticks un-interrupted get blood feeding for a long time.

It also determines the geographic distribution of the ticks and, consequently, become the risk areas for tick-borne diseases. This is particularly the case when ticks are vectors and reservoirs of the pathogens. Ixodes ricinus tick acts both as a vector and reservoir for a series of wildlife. A. Phagocytophilum and Theileria spp. are spread bandaged ixodid ticks remain attached to the skin of ungulates [5]. Some of these diseases are inflicted bites, scratches or licking. Some systemic infectious and parasitic diseases are transmitted from animals to humans and vice versa. Such a situation may lead to endemic problems in some communities [7]. Ticks and tick-borne pathogens found in multiple land-use types that are responsible for the easy transmission of disease pathogens [8]. The tick Immunobiology plays a significant role in establishing and transmitting many pathogens to their hosts [9] Hyalomma ticks on migratory birds [10]. Tick-borne diseases are also spread by companion animals like dogs and cats transported by humans (table 2). The risk of transmission of pathogen-infected ticks has increased substantially in recent decades due to the rise in tourist and economic migration rates.

The brown dog tick Rhipicephalus sanguineus, which is a vector of numerous pathogens causing diseases in animals and humans, is imported most frequently to many European countries from endemic areas in the Mediterranean region or from other parts of the world [11]. This spread of tick-borne viruses also increased in the last decade due to human movements and agricultural, tourism, trade and commerce. Besides this, environmental conditions also support the expansion of tick populations [12] (table 1). Although global warming is often cited as the underlying mechanism favoring the spread of tick-borne diseases, the climate has been just one of many factors that determine which tick species are found in a given geographic region.

Table 1: Important virus diseases transmitted by various tick species

S. No.	Disease	Organism	Vector	Geographical distribution	Symptom	Treatment	References
1	Eyach virus disease	Eyach virus (Ixodes ricinus)	Africa Central Asia Southern Europe	Rare	Biphasic fever, chills, headache, generalized musculoskeletal aches, and malaise.	Preventative measures include tick and mosquito repellents such as diethyltoluamide, physical barriers, and reduction of standing water.	[1]
2	Tick borne encephalitis	TBE virus complex Ixodes ricinus, Ixodes persulcatus	Europe Asia, Middle East	Common and widespread	Swelling of the brain and/or spinal cord, confusion, and sensory disturbances	no specific drug therapy for TBE	[14]
3	Crimean–Congohemorrhagic fever (CCHF)	(CCHF) virus (Hyalomma marginatum )other tick species	Europe Central Asia, India, Africa	Common and widespread increasing	Headache, high fever, back pain, joint pain, stomach pain, and vomiting.	Maintain fluid balance and correction of electrolyte abnormalities, oxygenation and hemodynamic support,	[27]
4	Powassan encephalitis	POW virus (Ixodes scapularis, Ixodes cookie)	Northern US/adjacent Canada far eastern Russia	Rare increasing	Swelling of the membranes surrounding the brain and spinal cord	No medication to treat Powassan virus infection.	[32]
5	Severe fever with thrombocytopenia syndrome (SFTS)	SFTS virus (Haemophysalis longicornis, Rhipicephalus microplus	China Korea Japan	Uncommon increasing	Thrombocytopenia, leukopenia, nausea, and vomiting	No prospective randomized studies on treatment strategies
6	Other TBEs Omsk hemorrhagic fever (OHF), Kyasanur Forest Disease(KFD) Louping ill virus, others	OHF virus KFD Louping ill virus (Ixodes Dermacentor, Haemophysalis)	Europe, Russia, China, Japan, India, Southeast Asia, Middle East	Rare to common within localized range some increasing	High-grade fever with chills, intense frontal headache, severe myalgia and body aches	no treatment	[32]
7	Heartland virus disease	Heartland virus (Amblyamma americanum)	Midwestern and Southwestern US	Rare	Fever, fatigue (feeling tired), decreased appetite, headache, nausea, diarrhea, and muscle or joint pain	No vaccines or medications to prevent or treat infection	[32]
8	Colorado tick fever	CTF virus	D. andersoni	?	Photophobia, vomiting, meningoencephalitis, and slight or partial paralysis.	no specific treatment for Colorado tick fever (CTF)	[32]
9	Meningoencephalitis	TBEV (FSME) virus,flavivirus	Deer tick(Ixodes persulcatus), Ixodes ricinus (Europe), Ixodespersulcatus	Europe and northern Asia	Meningitis	Supervision, bed rest, and other measures are important to prevent worsening symptoms	[32]
10	LSD (Lumpy skin disease)	LSD Virus	Cattle	?	Skin nodules and oedema, enlarged lymph nodes, nasal discharge	no treatment	[48]
11	Thogotovirus (THOV) disease, Dhori virus (DHOV)disease Bourborn virus disease	(THOV) (DHOV)disease Bourborn virus (Hyalommma, Amblyomma, Rhipicephalus)	Africa, Asia Europe, (THOV) (DHOV) USA, (Bourborn)	Rare, Bourborn virus isolated from Amblomma americanum	Meningitis and neuromyelitis optica	No specific treatment or vaccine
12	Bhanja virus disease	Dermacentor, Haemophysalis	Africa Central Asia Southern Europe	Rare	Fever, fatigue, pain	Acetaminophen	[88]

Table 2: Important bacterial diseases transmitted by various tick species

S. No.	Disease	Organism	Vector	Geographical distribution	Symptom	Treatment	Refrences
1	Lyme borreoliosis disease	Borrelia burgodorferi	Ixodes scapularis Ixodes pacificus Ixodes ricinus	North east, Midwest and west coast states, Europe, south-central U. S.	Erythema migrans, Fatigue, erythema migrans, malaisemyalgias, arthralgias, headache, fever chills	Amoxicillin) or cefuroxime Doxycycline (Vibramycin, non-steroidal anti-inflammatory drugs	[1]
2	Cowdriosis	Cowdria ruminant ium	Amblyoma varieg atum	Sub-saharan Africa	increased vascular permeability due to vascular endothelial cell invasion and consequent oedema and hypovolaemia: hyperaesthesia, aggression,	Sulphonamides and tetracyclines	[1]
3	Anaplasmosis	Anaplasma phago cytophilum	Ixodes scapularis Ixodes pacificus	North east, Midwest and west coast states	Myalgias, headache, fever chills	Doxycycline Chloramphenicol (Chloromycetin) Rifampin (Rifadin)	[1]
4	Anaplasmosis	Anaplasma platys	Rhipicephalus sanguineus	South central south western, U. S.	Myalgias,, headache, fever chills	Doxycycline Chloramphenicol Chloromycetin) Rifampin (Rifadin)	[1]
5	Southern rash illness	Borrelia	A. americanum	southern states and along the Atlantic coast as far north as Maine	Fever, headache, stiff neck, and mild muscle or joint pain.	(doxycycline)	[2]
6	Lyme disease	Borrelia	I. scapularis, I. pacificus	Northeastern United States. The upper Midwest	Fever, headache, chills, muscle and joint pain, fatigue	Amoxicillin, cefuroxime, and doxycycline.	[3]
7	Tick-borne Relapsing Fever	Borrelia species	Ornithodoros species ticks	Canada and Mexico United States,	Muscle pain, high fever, Headache, chills, vomiting and stomach pain	Doxycycline, Tetracyclin, erythromycin	[6]
8	Tick paralysis	Toxin	D. variabilis, D. andersoni	Argentina, Canada, and in several regions of the United States.	Muscle pain and feel tired and irritable	DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-menthane-diol, or 2-undecanon	[26]
9	Ehrlichiosis	Ehrlichiacanis	Rhipicephalus san guineus	South central south western, U. S	Myalgias,headache, fever chills	Doxycycline Chloramphenicol (Chloromycetin) Rifampin (Rifadin)	[32]
10	Ehrlichiosis	Ehrlichia ewingii, Ehrlichia,chaffeensispanola mountain Ehrlichia, sp	Amblyomma americanum	Cental and southeastern U. S. Extending northward along the atlantic coast	Myalgias, headache, fever chills	Doxycycline Chloramphenicol (Chloromycetin) Rifampin (Rifadin)	[32]
11	Ehrlichiosis	Ehrlichia muris	Ixodes scapularis	Upper Midwest (minnesota and Wisconsin)	Myalgias, headache,fever chills	Chloramphenicol Rifampin (Rifadin) (Chloromycetin)	[32]
12	Nairobi sheep disease	Bunyaviridae	Rhipicephalus appendiculatus	East and Central Africa Botswana and Mozambique. Asia, including India and Sri Lanka	Depression, anorexia, mucopurulent to hemorrhagic nasal discharge, occasional conjunctivitis, and fetid dysentery that causes painful straining.	no specific treatment,	[42]
13	Theileriosis	Theileria annulata, T. parva, T. hirci	H. anatolicum, R. appenticulatus	North Africa, southern Europe, the Near and Middle East, India	ever, swollen peripheral lymph nodes, pallour of mucous membranes, anaemia, nasal discharge, jaundice, salivation, rapid and shallow breathing, watery eyes	Tetracycline, buparvaquone	[45]
14	Babesiosis	B. equi	H. anatolicum	United States, Northeast and Midwest, Washington and California	Fever, chills, sweats. Malaise, fatigue. Myalgia, arthralgia, headache. Gastrointestinal symptoms, such as anorexia and nausea (less common: abdominal pain, vomiting) Dark urine	diminazene imidocarb azithromycin atovaquone clindamycin	[45]
15	African swine fever	African swine fever virus	Ornithodorus mobuta	Africa, Italian island of Sardinia. Belgium, Bulgaria, Lithuania, Poland and Romania.	High fever. Decreased appetite and weakness. Red/blotchy skin lesions. Diarrhea, vomiting. Coughing. Difficulty breathing.	No treatment or effective vaccine exists	[47]
16	Rocky mountain spotted fever	Rickettsia ricketsii	Dermacentor variabilis Rhipicephalus sanguineus, D. andersoni	Southcentral and southwestern and eastern U. S.	Myalgias,, headache, fever, malaise, vomiting, rash	Chloramphenicol tetracyclin Doxycycline	[47]
17	Tularemia	Francisella tularensis	Ixodes scapularis Amblyomma americanum Dermacentor variabilis	South and Midwest	Myalgias, headache, fever, chills, vomiting, fatigue, sore throat, abdominal pain, skin ulcers, diarrhea, S lymphadenopathy	Chloramphenicol Streptomycin Gentamicin,Tetracyclin, Fluroquinolones	[52]
18	Babesiosis	B. bigemina, B. ovis	R. (B.) microplus.	United States, Northeast and Midwest, Washington and California	Fever, chills, sweats. Malaise, fatigue. Myalgia, arthralgia, headache. Gastrointestinal symptoms, such as anorexia and nausea (less common: abdominal pain, vomiting) Dark urine.	diminazene imidocarb azithromycin atovaquone clindamycin	[58]
19	Babesiosis	B. motasi	Haemaphysalis spp	United States, Northeast and Midwest, Washington and California	Fever, chills, sweats. Malaise, fatigue. Myalgia, arthralgia, headache. Gastrointestinal symptoms, such as anorexia and nausea (less common: abdominal pain, vomiting) Dark urine	diminazene imidocarb azithromycin atovaquone clindamycin	[58]
20	Human Babesiosis	B. divergens	Ixodes spp.	United States, Northeast and Midwest, Washington and California	Fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia).	Atovaquone plus azithromycin clindamycin plus quinine.	[58]
21	African horse sickness	Reoviridae (African horse sickness virus)	Hyalomma dromedarii	Sub-Saharan Africa, Morocco, the Middle East, India, and Pakistan Iberian Peninsula and Thailand	Respiratory failure high fever, depression, and respiratory symptoms pulmonary edema, conjunctivitis dyspnea	No treatment or effective vaccine exists	[82]

Tick-borne virus encephalitis (TBE) a flavivirus [14] is the most important viral tick-borne live inside large number of wild and domestic animals [15]. TBE virus circulates in a complex cycle involving small mammals as amplifying hosts and ticks as vectors and reservoirs [16] These transmit pathogens include Anaplasma spp., Bartonella spp., Burkholderia spp., Francisella spp., Dera Ghazi Khan virus (DGKV), tick-borne encephalitis virus (TBEV), Lake Clarendon virus (LCV), Saumarez Reef virus (SREV), Upolu virus (UPOV), or Vinegar Hill virus (VINHV) (table 2). Humans can become infected by a tick bite and in some cases also by consumption of non-pasteurized raw milk and raw milk products from ruminants [18]. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes the co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia [19]. Most tick-borne viruses (TBV) are RNA viruses, some of which cause serious diseases in humans and animals worldwide [19]. Some of these viruses show non-viraemic transmission [19]. Ticks serve as important vectors of a variety of pathogens, mainly viral and prokaryotic. Vector competence is a component of bacterial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases [20].

Blacklegged tick, Ixodes scapularis is a major vector that transmits Lyme disease (Borrelia burgdorferi), human granulocytic anaplasmosis (Anaplasma phagocytophilum), and babesiosis (Babesia microti) [21]. Several human pathogens are transmitted by the blacklegged tick, Ixodes scapularis. These include the spirochetes [22]. Ixodes scapularis is currently known to transmit 7 pathogens responsible for Lyme disease, anaplasmosis, babesiosis, tick-borne relapsing fever, ehrlichiosis, and Powassan encephalitis. Ixodes scapularis can also be colonized by endosymbiotic bacteria, including those in the genus Rickettsia. Ixodes scapularis female nymphs are highly infective (table 2). High prevalence of infection and co-infection with multiple pathogens in Ixodes scapularis increased the public health consequences in an endemic area [23].

Viral diseases

Ticks transmit several human virus diseases in different eco-climatic zones of the world. A large diversity of ticks is detected from European, African and Asian countries. Among them are flaviviruses which are medically most important arboviruses reported from Europe and Asia. These causes between 10,000 and 15,000 human deaths annually in European countries alone [24] From European countries 6 medically important families are Flaviviridae, Bunyaviridae, and Reoviridae. In addition, three genera, flavivirus, nairovirus, and orbivirus, are the most prevalent [25]. Two new clouds of tick-borne phleboviruses, a mononega virus are also reported in Ixodes scapularis [26]. Among important diseases causing viruses are Flavivirus, tick-borne encephalitis virus, Omsk hemorrhagic fever virus, louping ill virus, Powassan virus, Nairovirus (Crimean-Congo hemorrhagic fever virus) and Coltivirus (each virus), which cause neurological diseases, hemorrhagic fever [27]. Most of the viruses are characterized from three species of ticks Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis [26]. Rhipicephalus microplus ticks contain huge virome diversity which is identified and reported from Hubei Province of China. Twelve RNA viruses with complete genomes were identified, which belonged to six viral families: Flaviviridae, Matonaviridae, Peribunyaviridae, Nairoviridae, Phenuiviridae, and [28]. Ticks transmitted by novel RNA viruses are also reported from Australia. Notably, three of these viruses clustered with known mammalian viruses, including novel cultivars that were related to the human pathogen Colorado tick fever virus [29] (table 2).

Tick-borne encephalitis

Ticks are important vectors for the transmission of pathogens, including viruses. Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) are highly pathogenic tick-borne flaviviruses. These are the leading cause of encephalitis that is an emerging disease spreading in many regions of Eurasia in dogs. Dogs become readily infected with the TBE virus, but they are accidental hosts not capable to further spread the virus. TBEV causes neurological disease in humans, while OHFV causes a disease typically identified with hemorrhagic fever [30].

Tick also harbors endogenous viruses and modulation of tick-borne pathogen growth. The viruses carried by tick’s also known as tick-borne viruses (TBVs), contain a large group of viruses with diverse genetic properties and are concluded in two orders, nine families, and at least 12 genera. Tick-borne encephalitis virus (TBEV) is a major arbovirus that causes thousands of cases of severe neurological illness in humans annually [31]. Ticks also transmit Powassan virus; a neurovirulent flavivirus that causes meningoencephalitis in North America and eastern Russia. Powassan virus disease displays severe neurological symptoms [32]. The main vectors of Powassan virus are Ixodes cookei, Ix. scapularis, Ix. marxi, Ix. spinipalpusm, Dermacentor andersoni, and D. variabilis. Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Ticks transmit viruses of flaviviridae virus family, mainly Kyasanur Forest Disease Virus (KFDV). Ticks transmit viruses of the flaviviridae virus family, mainly Kyasanur Forest Disease Virus (KFDV) (table 3). Ticks also transmit Tick-borne meningoencephalitis virus, a flavivirus spread by deer ticks (Ixodes scapularis), Ixodes ricinus (Europe), Ixodes persulcatus in Russia and Asia. This virus is endemic in Europe and northern Asia. Ticks also spread Colorado tick fever that is caused by Colorado tick fever virus (CTF), a coltivirus from the Reoviridae. Its transmission vector is Dermacentor andersoni in Western America. Crimean-Congo hemorrhagic fever is caused by CCHF virus, a nairovirus, from the Bunyaviridae and transmitted by Hyalomma marginatum, Rhipicephalus bursain Southern part of Asia, Northern Africa, and Southern Europe. Severe febrile illness is caused by Heartland virus, a phlebovirus, from the Bunyaviridae by Lone star tick (Amblyomma americanum) found in Missouri and Tennessee United States (table 3).

Table 3: Important protozoan diseases transmitted by various tick species

S. No.	Disease	Organism	Vector	Symptom	Treatment	References
1	Babeiosis	Babesia vogal	Rhipicephalus sanguineus	Severe headache, nausea, abdominal pain, hemolytic anemia, fever, chills, sweats	Atovaquone PLUS azithromycin, Clindamycin PLUS quinine	[1]
2	Babeiosis	Babesia gibsoni	Rhipicephalus sanguineus	Severe headache, nausea, abdominal pain, hemolytic anemia, fever, chills, sweats	Atovaquone PLUS azithromycin, Clindamycin PLUS quinine	[47]
3	Babeiosis	Other Babesia sp	Rhipicephalus sp.	Flu-like symptoms, body aches, loss of appetite, nausea, or fatigue	Antiparasitic drugs,	[47]
4	Hepatozoonosis	Hepatozoon americanum	Amblyomma maculatum	fever, lethargy, decreased appetite, weight loss, muscle pain/weakness, reluctance to move, and discharge from the eyes and nose	Trimethoprim-sulfa, clindamycin, and pyrimethamine.	[33]
5	Hepatozoon canis	Hepatozoon americanum	Rhipicephalus sanguineus	Haemolymphatic tissues and causes anaemia and lethargy.	Imidocarb dipropionate at 5-6 mg/kg IM and Tab. Doxycycline	[47]
6	Tularemia	Francisella tularensis	Ixodes scapularis Amblyomma americanum Dermacentor variabilis	cough, chest pain, and difficulty breathing, swollen lymph nodes near the skin ulcer	Streptomycin, gentamicin, doxycycline, and ciprofloxacin	[52]
7	Rocky mountain spotted fever	Rickettsia ricketsii	Dermacentor variabilis Dermacentor andersoni Rhipicephalus sanguineus	Fever, chills, or loss of appetite, nausea or vomiting, skin rashes or red spots, eye redness, headache, rash on the palms and soles, or sensitivity to light	Doxycycline, Monodox, Vibramycin,	[47]
8	Q Fever	Coxiella brunette	Dermacentor andersoni	Pain in the abdomen or muscles, fatigue, high fever, malaise, chills, or night sweats, coughing, headache, nausea, or shortness of breath	Antibiotic doxycycline	[39]
9	Ehrlichiosis	Ehrlichia chaffeensis	Amblyomma americanum, Ixodes scapularis	Human Monocytic plasmolysis, fever, chills, malaise, nausea, diarrhoea	Doxycycline	[51]
10	Anaplasmosis	Anaplasma phagocytophilum	Ixodes scapularis Ixodes pacificus	Human Granulocytic plasmolysis, fever, headache, chills, and muscle aches.	Doxycycline single IM injection of long-acting oxytetracycline at a dosage of 20 mg/kg.	[3]

Tick-borne paralysis

Tick-induced paralysis is the most widespread and dominant form of tick toxicoses is caused by Amblyomma aculatum on the Mexican Pacific Coast [33]. Australian paralysis is caused by tick Ixodes holocyclus [34]. This tick species secrete toxins which produce positive inotropic responses in rat left ventricular papillary muscles and positive contractile responses in rat thoracic aortic rings [34]. Destruxin A secreted by Rhipicephalus (Boophilus) microplus ticks (Acari: Ixodidae) causes tetanic paralysis [35]. Tick secrete a highly paralytic and lethal venom cocktail of proteinaceous molecules contain neurotoxins HT-1, present in the saliva ticks despite several species possessing saliva of the Australian paralysis tick [36] (table 3).

Protozoan diseases

A huge diversity of ticks that spread tick-borne protozoan diseases in livestock are reported Middle East and North Africa [37]. Protozoans i.e. Babesia divergens, B. venatorum, and B. microti have also been detected in urban tick Ixodes ricinus populations in Europe [38]. Six ticks, including Amblyomma triguttatum, Bothriocroton hydrosauri, Haemaphysalis novaeguineae, Ixodes cornuatus, Ixodes holocyclus, and Ixodestasmani transmit Coxiellaburnetii, Rickettsia australis, Rickettsia honei, or Rickettsia honeisubspmarmionii. These bacterial pathogens cause Q fever, Queensland tick typhus (QTT), Flinders Island spotted fever (FISF), and Australian spotted fever (ASF) [39] (table 4).

Theileriais is caused by economically important, intra-cellular protozoa, which is transmitted by ixodid ticks. It infects both wild and domestic ruminants. In the mammalian host, parasites infect leukocytes and erythrocytes. Theileria sporozoites immortalize and transform host cells of haematopoietic origin [40]. Theileria annulata is a tick-transmitted protozoan parasite of cattle, which transforms cells of macrophage (Mphi) or B cell lineage [41]. Theileria parva, undergoes obligate sexual stage development in its tick vector Rhipicephalus appendiculatus. R. appendiculatus ticks are able to acquire T. parva parasites from infected cattle even in the absence of detectable parasitemia. T. parva transmission by R. appendiculatus is seen in East Cost Fever endemic regions [42]. Buffalo (synceruscaffer) are the natural host of Theileria parva, mainly non-diapausing populations of R. appendiculatus that was introduced from eastern Africa with cattle imported in 1901 [43]. Recombinant forms of Theileria parva and Theileria annulata sporozoite surface antigens induce protection against parasite challenge in cattle [44].

East Coast fever (ECF) is a devastating disease of cattle and a significant constraint to the improvement of livestock production in sub-Saharan Africa. The protozoan parasite Theileria parvais the etiologic agent of East Coast fever, an economically important disease of cattle in sub-Saharan Africa. East Coast fever (ECF) is a devastating disease of cattle and a significant constraint to the improvement of livestock production in sub-Saharan Africa. The protozoan parasite Theileria parvais the etiologic agent of East Coast fever, an economically important disease of cattle in sub-Saharan Africa. Theileria parva causes theileriosis infection of H. anatolicum with T. lestoquardi. Theileria parvais transmitted by the ixodid tick Rhipicephalus appendiculatus, is the cause of East Coast fever (ECF) [43]. This protozoan parasite is biologically transmitted by Rhipicephalus appendiculatus (Neumann) (Acari: Ixodidae) Babesiosis [45] (table 4).

The black-legged tick, Ixodes scapularis, is the primary vector to humans that transmit the protozoan parasite Babesia microti [46]. Ticks spread infection of bacterial genus Rickettsia mainly typhus, rickettsialpox, boutonneuse fever, African tick bite fever, Rocky Mountain spotted fever, Flinders Island spotted fever, and Australian tick typhus [47] (table 4).

Table 4: Important fungal diseases transmitted by various tick species

S. No.	TBDs	Species	Host	Vector tick species	Symptoms	References
1	Anaplasmosis	Anaplasma phagocytophilum, A. platys, A. marginale, Abovis, A ovis, A central	Ruminants, dogs, human	Ixode spp, Dermacentor spp, Rhipicephalus spp, Haemaphysalis spp, Hyalomma spp, Ornithodorus spp	Human Granulocytic plasmolysis, fever, headache, chills, and muscle aches	[1]
2	Mediterranean spotted fever	Rickettsia canarii complex (Rhipicephlus sanguineus)	Man	Dog tick Rhipicephalus sanguineus	Headache, fever and maculopapular rash	[11]
3	Ehrlichiosis	Ehrlichia canis	Dogs	Rhi. Sanguineus?	Human Monocytic plasmolysis, fever, chills, malaise, nausea, diarrhoea	[32]
4	CCHF	CCHF virus	Human	H. marginatum, haemaphysalis spp, Rhipicephalusspp, I. ricinus	Stomach pain and vomiting. Red eyes, a flushed face, a red throat, and petechiae	[32]
5	Pacific Coast tick fever	Rickettsia philipii (Dermacentor occidentalis)	Horses, deer, cattle, lagomorphs, peccaries, porcupines, tapirs, desert bighorn sheep, and humans	Dermacentor species	Eschar or tissue necrosis	[33]
6	Theileriosis	T. annulata, T. buffeli/orientalis/sergenti, T. ovis, T. equi	Ruminants equid	H. marginatum, H. anatolicum, Hexcavatum, H detritum, Haemaphysalis spp, Rhipicephalus	Anemia and, in some cases, jaundice or hemoglobinuria.	[43]
6	Rocky Mountain Spotted fever	Rickettsia rickettsia (Dermacentor variabilis, Dermacentorandersoni)	Man, Dog, small mammals are the natural reservoirs in the wild	Dermacentor variabilis and Dermacentor andersoni.	Subclinical infection to severe or fatal multiorgan collapse. Blackened or crusted skin at the site of a tick bite.	[47]
7	African tick bite fever	Rickettsia africae (Amblyomma)	Ruminants, equids, candis, felids, rodents, human	Rhipicephalus annulatus, Rhi. Bursa, Rhituranicus, Rhisanguineus, Hyalomma excavatum, H rufipes, H marginatum, H. dromedarii, Haemaphysalis punctate, Haeparva, Hae. sulcata, Dermacentor marginatus, D. reticulatus, Ixodes ricinus	Severe headache, nausea, abdominal pain, hemolytic anemia, fever, chills, sweats	[47]
8	Cytauxzoonosis	Cytauxzoonfelis	Domestic cat	star tick, Amblyomma americanum	Necropsy, splenomegaly, hepatomegaly, enlarged lymph nodes, and renal edema
9.	Bartonellosis (Cat scratch fever)	Bartonella henselae	Cat	?	Fever, headaches, fatigue, poor appetite, brain fog, muscle pain, and swollen glands around the head, neck, and arms.
10	Hepatozoonosis	Hepatozoon canis	Candis felids	Rhi. Sanguineus	Fever, lethargy, decreased appetite, weight loss, muscle pain/weakness, reluctance to move, and discharge from the eyes and nose
11	Aegypti anellosis	Aegyptianella pullorum	Duck	?	Parasitize the erythrocytes, infectious anemia”.
12	Tick-borne typhus	R. hoogstraali, R. aeschlimanni, R. slovaca	Human Dogs	H. marginatum, H. aegyptium, H excavatum, D. marginatus, Haeparva	High fever, nausea, malaise, diarrhea, and vomiting.
13	Tularemia	Francisella tularensis	Human	?	cough, chest pain, and difficulty breathing, swollen lymph nodes near the skin ulcer	[52]
13	Candidatus R. vini	R. vini	Birds	Ixodes arboricola, Haemaphysalis longicornis ticks	Leukopenia and elevated hepatic enzyme levels	[58]
14	Rickettsiosis	Rickettsia parker (Amblyommam aculatum)	Small mammals and humans	Dermacentor variabilis Dermacentor andersoni Rhipicephalus sanguine	Rickettsial vasculitis, vascular inflammation	[63]
15	Lyme Borreliosis	Borrelia burgdorferi, Bor. Turcica sp. Nov	Human, dogs, horses	I. ricinus, H. aegyptium, H excavatum, D. marginatus, Haeparva	Circular rash with red oval or bull’s-eye marks appear anywhere on the body, fatigue, joint pain and swelling, fever, swollen lymph nodes	[64]
16	Canine filariosis	Acanthocheion emareconditum	Dogs	?	Weight loss, cough, fatigue	[75]
	Dermatophytosis	Trichophyton spp, M gypseum, and less commonly M canis	human and animal	Rhipicephalus microplus	the dermatologic disease of nails, skin and hair	[89]
	Histoplasmosis	Histoplasma capsulatum	human and animal	Ticks andbadger	Body ache, fever, chills, resemble those of the flu.	[91]
	Ring worm Dermatophilosis	Dermatophilus congolensis	horses, cattle, sheep, goats and humans.	Ixodes	Red, scaly and itchy patches, hair loss	[91]
	Conidiosis	Metarhizium spp. Beauveria bassiana	human and animal	Rhipicephalus microplus	fever and chills	[92]
17	TBRF	Bor. Crocidurae	Rodents	Ornithodoro serraticus	Fatigue, fever, loss of appetite, malaise, night sweats or sweating, loss of muscle, phlegm, severe unintentional weight loss, shortness of breath, or swollen lymph nodes
18	Hemoplasmosis	Mycoplasma haemofelis	Cat	?	Lethargy, weakness, reduced appetite, dehydration, weight loss and intermittent pyrexia

Lumpy skin disease

The Lyme disease-causing organism, Borrelia burgdorferiis transmitted into the mammalian host by an infected-tick bite Lumpy skin disease (LSD). This causes economic losses to the cattle industry in Africa and the near and Middle East. Ixodid ticks include the genera Rhipicephalus (i.e., brown dog tick), Dermacentor (i.e., American dog tick, Rocky Mountain wood tick, Pacific or West Coast ticks), Ixodes (i.e., shoulder tick of North America, deer tick, British dog tick [Europe]), Amblyomma (i.e., black-legged tick, Lone Star ticks), and Haemophysalis (i.e., yellow dog ticks [Africa and Asia]) and cause lumpy skin disease (table 4).

Bacterial diseases

Ticks harbor and, in many cases, transmit to their vertebrate hosts, a wide variety of pathogenic, pathogenic and endosymbiotic microorganisms. Ticks are the most important vectors of human pathogens, mainly the emergence of Lyme disease and human ehrlichiosis, respectively [51]. Lyme disease is caused by Borrelia burgdorferi, its 15 forms have been identified throughout the world, including 8 rockets, 3 ehrlichiae, and 4 species. Important tick-borne bacterial diseases are rickettsioses, ehrlichioses Lyme disease, relapsing fever braless, tularemia, Q fever, particularly those regarded as emerging diseases. Tick bites transmit bacteria which is a biggest challenge for clinicians [52]. The obligate intracellular bacterium Ehrlichia ruminantium (ER) causes hot water, a fatal tick-borne disease in livestock [53]. Ehrlichia chaffeensis is a tick-transmitted obligate intracellular pathogenic bacterium which causes human Monocytic ehrlichiosis and putative host cell targets during infection [54]. Tick-borne relapsing fever is evoked by spirochetes which are blood-borne pathogens transmitted through the saliva of soft ticks [55]. Ticks cause multiple bacterial diseases, including Anaplasma phagocytophilum (anaplasmosis), Borrelia burgdorferi and Borrelia mayonii (Lyme disease), Borrelia miyamotoi (relapsing fever-like illness named Borrelia miyamotoi disease), and Ehrlichia muriseauclairensis (a minor causative agent of ehrlichiosis) It also transmits Borrelia burgdorferi (sensustricto) in eastern North America [56]. Ticks Ixodes scapularis and Ixodes ricinus are infected by Borrelia burgdorferis. S. Ehrlichia ruminantium. Ixodes ricinus is the principal vector of the largest variety of microorganisms, bacteria and piroplasms [57]. High prevalence of ticks infected with Borrelia burgdorferis. cause Lyme borreliosis. This disease is prevalent in urbanized areas in Europe. Other important emerging pathogens, including bacteria of the order Rickettsiales (Anaplasma phagocytophilum, “Candidatus Neoehrlichia mikurensis,” Rickettsia Helvetica, and R. monacensis), and Borrelia miyamotoi (table 4).

Tick-borne babesiosis

Tick-borne babesiosis is an emerging zoonosis. This is a well-recognized malaria-like disease that occurs worldwide [58]. Babesiosis is an important tropical tick-borne haemoprotozoan disease occurs in dogs. Babesiosis is a potentially life-threatening illness caused by intra-erythrocytic protozoan parasites of the genus Babesia. This pathogen is transmitted most commonly by Ixodes ticks, it also rarely occurs through blood transfusion or congenitally. This is clinically manifested by anorexia, dehydration, temperature, dullness/depression, diarrhea/constipation, pale mucosa, hepatomegaly, vomiting/nausea, splenomegaly, distended abdomen/associates, yellow colored urine, emaciation/weight loss, and ocular discharge [59]. Antibiotics such as atovaquone plus azithromycin or clindamycin and quinine are used to treat this disease. The disease causes heavy mortality in high-risk populations in spite of anti-biotic therapy [60]. Development of modern molecular tools led to the discovery and identification of emerging or new tick-borne microorganisms, mainly tick-borne pathogenic bacteria and symbionts with unknown zoonotic potential [61]. A small bacterial diversity which infests livestock across reported from tick species was identified on the basis of bacterial 16SrRNA [62]. The most important genera identified are Ralstonia, Clostridium, Staphylococcus, Rickettsia, Lactococcus, Lactobacillus, Corynebacterium, Enterobacter, and Enterococcus. The Candidatus Rickettsia emblem is reported in Rhipicephalus microplus, Hyalomma anatolicum, and H. dromedary tick species. These also carry T. emulates [62].

Lyme borreliosis (LB) spirochetes have been isolated tick cell lines, primary cell cultures and organ cultures and adult Ixodes ricinus, Dermacentor marginatus and Dermacentor reticulatus ticks. Camels and/or the ticks infesting them are disease reservoirs of zoonotic Q fever (C. Burnett), ehrlichiosis (E. chaffeensis) and rickettsiosis (R. africae), which pose public health threats to pastoralist communities [63]. Amblyomma ticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogen Ehrlichia ruminantium in sub-Saharan Africa [64]. Rickettsia spp., Babesia spp., Anaplasma marginale, Anaplasma spp. and Coxiella-like organisms have been identified in one-humped camels (Camelusdro medarius) in Nigeria [65] (table 4).

Members of the genus Spiroplasma are Gram-positive bacteria without cell walls. Some Spiroplasma species can cause disease in arthropods such as bees, whereas others provide their host resistance to pathogens [66]. The presence of the bacteria in the tick eggs used to initiate the primary cultures confirms that transovarial transmission of this Rickettsia occurs [67]. Spiroplasma ixodetis and the Mycobacterium isolate belonged to the Mycobacterium chelonae are also identified [68]. Babesia gibsoni transmitted by larval progeny of Haemaphysalis longicornis and H. hystricisticks and B. vogeli from larvae of R. sanguineus have been isolated [69].

Anaplasmosis

Anaplasmosis is an emerging zoonotic disease with a natural enzootic cycle. This disease is spread by Ixodes ricinus and Ixodes scapularis are the principal vector of Anaplasma phagocytophilum. Anaplasma phagocytophilum causes human granulocytic anaplasmosis, one of the most common tick-borne diseases in North America. This unusual obligate intracellular pathogen selectively persists within polymorphonuclear leukocytes. Tick also transmits Tofla virus; a Nairovirus of the Crimean-Congo hemorrhagic fever group found in Japanese ticks.

Ixodes scapularis transmits a group of pathogens, including Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum, the causative agents for Lyme disease, Babesiosis, and anaplasmosis, respectively. Lyme disease is transmitted by I. scapulars that impose significant implications regarding clinical diagnosis, and treatment in human population in an endemic area [70].

The ixodid genus includes important disease vectors of animals and humans. Ticks transmit disease organisms such as the bacterium Borrelia burgdorferi that causes Lyme disease and tick-borne encephalitis (TBE) virus through saliva. In addition, the protozoan Babesia and the bacterium Anaplasma cause diseases in livestock. Rocky Mountain spotted fever, a systemic tick-borne illness is caused by an obligate intracellular bacterium Rickettsia rickettsii. This is associated with widespread infection of the vascular endothelial [71] Ticks carry zoonotic disease viruses from animals to humans and generate severe health-related consequences to man, livestock, dogs, sheep, cows, buffaloes, antelopes, horses, ferrets, and cats [72] (table 4).

Lyme disease

Ticks are also responsible for the transmission of several animal and human pathogens, including the causal agents of Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis and human babesiosis [73]. Lyme borreliosis (LB) and other Ixodes ricinus-borne diseases (TBDs) are diseases that emerge from interactions of humans and domestic animals with infected ticks in nature [74]. Ixodid ticks are notorious blood. sucking ectoparasites and are completely dependent on blood meals from the hosts. Lyme paralysis is caused by Ixodes-tick transmitted spirochete Borrelia burgdorferi consulate bacteria transmitted to humans by the bite of hard ticks, Lyme disease is the commonest worldwide [75]. This disease is a potential health threat to Canines, mainly dogs and lives stocks. It manifests with arthritis-induced lameness, anorexia, fever, lethargy, lymph adenopathy and, in some cases, fatal glomerulo–nephritis. The Lyme disease parasite Borrelia burgdorferi, possesses a number of outer membrane proteins that are differentially regulated during its life cycle. During natural infection with the agent of Lyme disease, Borrelia burgdorferi, spirochetes are delivered with vector saliva, which contains anti-inflammatory and antihemostatic activities [76]. The vaccine could be an efficient approach to decrease Lyme disease incidence. Lyme disease transmission, with the purpose to highlight various aspects in the ecological cycle of disease transmission to be incorporated, including the growth of ticks with different stages in the life cycle, the seasonality, host diversity, spatial disease pattern. Due to host short distance movement and bird migration, co-infection with other tick-borne pathogens, and climate change impact [77]. Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease [78]. Lyme borreliosis patients show variable clinical manifestations, i.e. pruritus, swollen joint, pain, lymphadenopathy and ulceration, respectively [79]. For control of Lyme borreliosis and other Ixodesricinus-borne diseases multidisciplinary approaches ecological, medical, veterinary and cultural must be required. Lyme borreliaeproteins promote vertebrate host blood-specific spirochete survival in Ixodesscapularis nymphs using artificial feeding chambers. BBA52 and Lp6.6 protein play an important role in promoting spirochete survival in nymphal ticks fed on human or quail blood. The ability of spirochetes to survive in ticks during blood feeding is thought to be essential for Lyme borreliae to be transmitted to different vertebrate hosts. Identification of Lyme borreliaeproteins promoting vertebrate host blood-specific spirochete survival in Ixodesscapularis nymphs using artificial feeding chambers [80]. Lyme disease in caused by Borrelia buisensulatorgdorferi. There are various parallel proteins which directly or indirectly contribute to the natural cycle of B. burgdorfer iinfection. There is a need to identify discrete molecular interactions between spirochetes and tick components, which play critical roles in pathogen persistence and transmission by the arthropod vector [81] (table 4).

Rickettsioses

Rickettsioses have epidemiological importance that includes pathogens, vectors, and hosts are caused by dog tick Rhipicephalussanguineus and the camel ticks Hyalommadromedarii. These are important vectors and reservoirs of Rickettsiae vectors of Rickettsioses (Acari: Ixodidae) infected male ticks do sexual transmission of spotted fever group rickettsiae. Rickettsiae have been detected in spermatogonia, spermatocytes, and maturing spermatids [82]. Common marmosets are susceptible to a number of bacterial infections, which may be exotic, causing sporadic but occasionally severe disease. They secrete potential toxic molecules in the blood remains Ixodid ticks, in combination with the bacterial transmission; induce a robust inflammatory response at the blood-feeding site. Hard Tick Amblyomma variegatum causes theileriosis is a blood piroplasms disease that adversely affects livestock, especially in tropical and sub-tropical countries. It is caused by haemoprotozoan found in hard ticks. Tick-borne pathogens (TBPs), especially Anaplasma phagocytophilum, cause disease in grazing livestock. Human seven-trans-membrane (7TM) G protein-coupled chemokine receptor is a large family of leukocyte chemoattractant receptors. It regulates immune system development and function, in large part by mediating leukocyte trafficking during infection or wound healing. Borrelia spp. generates production of four inflammatory cytokines. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering the vertebrate host skin occurs with local antigen-presenting cells. While to, tick-associated Borrelia sp. evoke pathogens cytokine responses in THP-1-derivedmacrophages after exposure to selected borreliae, including a non-pathogen [83]. It is a multiprotein complex (T4Es) that allows the bacteria to evade host defenses and, to subvert host cell processes to their own advantage [84] (table 4).

Endosymbionts in Soft ticks

Ticks Bacterial endosymbionts of ticks are of interest due to their close evolutionary relationships with tick-vectored pathogens. For instance, whereas many ticks contain Francisella-like endosymbionts (FLEs), others transmit the mammalian pathogen Francisellatularensis [85]. D. Variabilis is normally resistant to entomopathogenic fungus Metarhizium anisopliae. Female ticks harbor S. brevicaulis a mycobiont internally [86]. Coxiella burnetii, the logic agent of acute Q fever and chronic endocarditis, is an intracellular form that occupies a large lysosome-derived acidic vacuole. C. burnetiia bacterium grows with in mammalian cells obligate intracellular replication in a hostile manner [87]. Ixodes scapularis and Dermacentor andersoni, infected with an endosymbiont, Rickettsia peacockii Lyme disease spirochete, Borrelia burgdorferi. Rickettsia peacockii non-pathogenic obligate intracellular bacterium found as an endosymbiont in Dermacentor andersoni ticks in the western USA and Canada. Its presence in ticks is correlated with the reduced prevalence of Rickettsia rickettsii, the agent of Rocky Mountain spotted fever [88].

Fungal diseases

Although there are over 250 zoonotic diseases, only 30-40 of them involve dogs and cats. Transmission of zoonotic infections occurs via bites, scratches or touch; exposure to saliva, urine or faeces; inhalation of particles or infectious aerosols; contact with a transport or intermediate host (e. g., ticks, fleas); or exposure to contaminated water, soil or vegetation. This paper summarizes the most important common zoonotic dermatological diseases of dogs and cats. The most common dermatological sinuses are flea and tick infestations and the diseases they transmit; dermatophytosis; and mite infestations (Sarcoptes and Cheyletiella). Prevention of zoonotic infestations or infections can be accomplished easily by the use of routine flea and tick control, screening of new pets for dermatophytosis, and routine hand-washing [89] Pets like dogs and cats are responsible for a series of sonatas disorders. Pets like dogs and cats are responsible for a series of sonatas disorders. Some of these diseases are inflicted bites, scratches or licking. Others result from a close contact with fur, or are transmitted by osteoporosis or by the contaminated environment. Some systemic infectious and parasitic diseases are transmitted from animals to humans and vice versa. Such a situation may lead to endemic problems in some communities.

Fungal infections associated with zoonotic spread are an important public health problem at global. There are numbers most common fungal diseases, such as: dermatophytosis, sporotrichosis, and histoplasmosis, which are seen in humans [90]. Histoplasmosis is a fungal disease associated with bat guano (stool) (CDC0 and is a type of lung infection. It is caused by inhaling Histoplasma capsulatum fungal spores. Coccidioidomycosis is an infection usually caused by inhaling the spores (“seeds”) of either Coccidiodes immitis or Coccidioides posadasii fungi). Ticks are vectors or reservoirs in the transmission of pathogenic fungi such as (Dermatophilosis) [91]. M. anisopliae sensulato and Beauveria bassiana infect tick cuticle that further transmit this fungi to humans [92]. Diagnosis of tick saliva disease pathogens Ticks are blood-sucking arthropods which largely affect host health, mainly vertebrate host’s and affect hemostasis, cause inflammation, and weaken immunity [93]. Tick salivary gland secretions contain a diversity of pathogens, including viruses, bacteria and eukaryotes [94]. Ticks used saliva during blood sucking as an anti-coagulant and release several types of pathogens into the host blood. It makes them versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding [95].

Tick saliva is increasingly recognized as a rich source of bioactive molecules with specific functions. Ticks use their saliva to overcome the innate and adaptive host immune systems. Their saliva is a rich cocktail of molecules, including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. So many salivary gland molecules that work as antigens have been isolated from tick saliva. These have been characterized and shown to be promising candidates for drug development for vertebrate immune diseases. Salivary proteins are part of the host-tick interface and play vital roles in the tick feeding process and the host infection by tick-borne pathogens. These could be used as important targets for immune interventions. Transcriptome provides a valuable reference database for ongoing proteomics studies of the salivary glands [96].

Tick salivary compounds are of immense immune-pharmacological importance of non-coding RNAs that might be exploitable as immunomodulatory therapies [97]. The majority of salivary secretion substances are expressed by the parasite salivary gland and secreted in tick saliva. Characterization of cattle ticks salivary gland gene expression in tick-susceptible and tick-resistant hosts may be helpful in putative targets for the control of tick infestations. These genes might be involved in the mechanism of stress response during blood feeding [98]. Natural infection of TBEV and WNV can be identified by cross-reactive ELISAs screening [99] and confirmed by serum neutralization tests [100]. Analysis of the secondary protein structures using FTIR-ATR show both in vivo and membrane-fed cement cones contain βsheets, but only in vivo cement cones contain helical protein structures. Proteomic analysis is used to identify both secreted and non-secreted tick proteins [101]. Sialotranscriptomics is used for proteomics studies of the salivary glands and saliva of various tick species. The bacterial diversity across these tick species was assessed by bacterial 16S rRNA gene sequencing using a 454-sequencing platform about 10 of the different tick species infesting livestock [102]. BLSOM program is used to know phylogenetic relationships based on the similarity of oligonucleotide frequencies and functional annotation by BLASTX similarity searches [103].

BLSOM analysis is used to detect microorganisms belonging to the phylum chlamydia in some tick species. These could be identified by new methods by selectively amplify microeukaryote genes in tick-derived DNA by blocking the amplification of the 18S rRNA gene of ticks. Using artificial nucleic acids, mainly peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). Additionally, the PNA-or LNA-based methods were suitable for pancreatic analyses, whereas the UNonMet-PCR method was particularly sensitive to fungi [104]. For detection of TBE virus and Bluetongue virus in ticks and real-time RT-PCR is also done [105] Indirect immunofluorescence is applied for detection of Borrelia spirochetes [106]. The ELISA test is also used for viral purified nucleoprotein for virus infection [107]. Tick-borne zoonotic infections are among the most diffuse vector borne diseases. These are caused by different microorganisms: Babesia spp., Borrelia spp., Rickettsia spp., Ehrlichia spp., Francisella tularensis, Coxiella burnetii) and tick-borne encephalitis virus. Babesiosis is caused by the protozoa (sporozoa) Babesiamicroti. This is quite rare in humans in Europe. Lyme borreliosis caused by the spirochete Borrelia burgdorferi. This is identified by using PCR assay [108]. OspA-based PCR on cerebrospinal fluid (CSF) samples from patients with Lyme neuroborreliosis. Besides this, DNA sequence analysis and PCR assays is perfomedon the amplicon to determine the genospecies of Borreliapresent in the CSF [109]. The microbiological diagnosis is also done by serologic techniques (IFA, EIA, WB) and by mainta in vitro culture of microbes and DNA amplification methods [110]. In vitro culture is also done in isolation of microbial antigens that increased the diagnostic sensitivity and accuracy in clinical isolates [111] (table 4).

16S rRNA gene sequences are considered as good markers of the presence of the internal microbiome of tick, mainly Cayenne tick Amblyomma cajennense (since strict). Surface sterilization methods are used for studying internal micro biodiversity [112]. The variety of Borrelia burgdorferi sensulato (B. burgdorferi) genospecies leads show differences in clinical isolates of Lyme borreliosis (LB). In addition, Lyme Borreliageno species were subsequently identified by sequence analysis and real-time polymerase chain reaction (PCR) amplification of the 16S rRNA gene [112]. Tick Microbiomes for Borrelia species in Ixodes ricinus show differences. These can be identified by using sequence analyses of the 16S rRNAgene [113]. Borrelia burgdorferi genospecies in Ixodes ricinus ticks were also identified by using by dark field microscopy (DFM) [114]. PCR method was applied, in which a fragment of the flu gene was used as a marker [115]. Borrelia species transmitted by hard ticks bacteria in ixodid ticks infesting domestic animals were identified by using quantitative (q) real-time PCR followed by standard PCR and sequencing to identify the species [116]. Real-time PCR targeting based on the ospA gene was used for the detection of Borrelia burgdorferi sensustricto, Borrelia garinii, Borrelia afzelii and Borrelia valaisiana [117]. PCR also used to find differences in various disease biotypes of spirochaetes an agent of Lyme disease [118]. Borrelia sp. In an Amblyomma varanense was collected from snake Python reticulates [119] (table 4. Discrete molecular interactions between spirochetes and tick components also have been discovered by using DNA-based molecular markers. These play critical roles in pathogen persistence and transmission by the arthropod vector. In addition, various antigens of immuno-pharmacological importance were isolated from tick salivary glands. In addition, sequence analysis was done for identifying non-coding RNAs that could be used in immunomodulatory therapies.

Control of ticks

Ticks are important human and animal parasites and vectors of many infectious diseases Control of tick activity is an effective tool to reduce the risk of contracting tick-transmitted diseases. For tick control generally, conventional acaricides are used [120]. For tick control oral treatment of pet is doing. For this purpose oral administration of afoxolaner (NexGard™) and fluralaner (Bravecto™) with topically applied permethrin/imidacloprid (Advantix®) was followed to check transmission of Ehrlichia canis by infected Rhipicephalus sanguineus ticks to dogs.

For tick control oral treatment of pet is doing. For this purpose oral administration of afoxolaner (NexGard™) and fluralaner (Bravecto™) with topically applied permethrin/imidacloprid (Advantix®) was followed to check transmission of Ehrlichiacanis by infected Rhipicephalus sanguineus ticks to dogs. Advantix® effectively blocked the transmission of E. canis to dogs and provide adequate protection against monocytic ehrlichiosis [121]. In ticks, the attraction–aggregation–attachment, assembly may be controlled by ticks host kairomones. For safe control of ticks lure-and-kill and lure-enhanced biocontrol strategies based on employmentof various pheromones were also tried [122]. For better control establishing inter-relationship between ticks and the pathogens is highly important. It will provide idea about the mechanisms of acquisition, persistence and transmission patterns in various hosts. For successful control of ticks molecular drivers for tick-borne diseases, mainly responsible for tick-pathogen molecular interactions of bacteria, viruses, and protozoa affecting human and animal health are to be studied.

The tick immunobiology plays a significant role in establishing and transmitting many pathogens to their hosts. Anti-tick vaccines could interrupt blood-feeding ticks; this might be a good method for tick control [123]. For control of black-legged ticks rodent-targeted oral vaccines against B. burgdorferi and rodent-targeted antibiotic bait are also used. Besides this, new explorations be made for finding new potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against a wide range of hard and soft ticks [124]. Protease inhibitors (PIs) that primarily target serine protease-mediated pathways also disrupt blood feeding [125]. Non-pathogenic microorganisms may also play a role in driving transmission of tick-borne pathogens (TBP), with many potential implications for both human and animal health [126].

Larval tick abundance increases the prevalence, and incidence Lyme disease. For cultural control of ticks, spatially diffuse space, including backyards, neighbourhood green spaces, and public recreation areas must be regularly treated with anti-tick formulations In addition, stone walls, wood chip barriers separating the lawn from adjacent forest, bird feeders, fencing, wood stores, and prevalence of bushy plants must be removed. Massive tick control could be achieved by controlling the emergence and the movements of larval tick. More often, larval tick abundance increase the prevalence of disease incidence. Therefore, the presence or absence of pets and outdoor animals must be fully checked. For successful control of ticks, all host animals must be shifted to clean places and old places must be treated routinely. For driving the massive control ticks’ new alternative methods must be developed to check the tick infection. For this purpose natural cycle of ticks, and tick-parasite dynamics must be studied. In addition, various aspects in the ecological cycle of disease transmission to be incorporated, including the growth of ticks with different stages in the life cycle, the seasonality, host diversity, spatial disease pattern due to host short distance movement and bird migration, co-infection with other tick-borne pathogens, and climate change impact.

For control of ticks identification of critical elements of the pathogens’ lifecycle is highly important [127]. There has been increasing trends in disease occurrence and movement associated with the global movement of humans and global trade of animals. Hence, for the successful control study of tick ecology and tick born-disease transmission and vaccination are equally important integrated tick management consists of the systematic combination of at least two control technologies can reduce selection pressure in favor of acaricide-resistant individuals, while maintaining adequate levels of animal production [128]. Disease control and prevention could be achieved effectively through good integration between public health, veterinary medicine and animal management, and ecological approaches. For successful management mitigation of tick-associated negative social effects is highly essential [129]. Responsibility will be distributed to individual persons and professionally staffed tick-management programs [130]. To reduce the risk, disease burden and costs of TBDs both environmental and health policies must be implemented at a global level for mitigation of tick associated morbidities and economic loss [131, 132].

CONCLUSION

Ticks are major ecto-paraistesof animal hosts, which transmit large numbers of pathogenic infectious agent’s virus, bacteria, protozoans and fungi which generate various zoonotic diseases in man and dairy farm animals or livestock. The sole source of transmission of infection is tick saliva that assists them in blood feeding by inhibiting blood coagulation. Ticks borne diseases severely affecting human health and are more dangerous than envenomation. Ticks saliva is a rich cocktail of molecules, including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. So many salivary gland molecules that work as antigens have been isolated from tick saliva. These have been characterized and shown to be promising candidates for vaccine production and drug development. Tick control is possible by searching new potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against a wide range of hard and soft ticks Protease inhibitors primarily target serine protease-mediated pathways can be used for disruption of blood feeding. Plant repellents, herbal formulations, oils, poison baits and cultural control of ticks can reduce their population. For control of ticks identification of critical elements of the pathogens’ lifecycle is highly important. Disease control and prevention could be achieved effectively through good integration between public health, veterinary medicine and animal management, and ecological approaches. For successful management mitigation of tick-associated negative societal effects is high essential. Responsibility will be distributed to individual persons and professionally staffed tick-management programs. To reduce the risk, disease burden and costs of TBDs both environmental and health policies must be implemented at a global level for mitigation of tick-associated morbidities and economic loss.

ACKNOWLEDGEMENT

Nidhi Yadav is thankful to DST for DST/INSPIRE Fellowship/[IF190957] awarded by Department of Science and Technology Ministry of Science and Technology, Government of India, wide letter dated 3^rd September 2021. Authors are thankful to H. O. D., Department of Zoology for research facilities.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

Ravi Kant Upadhyay and Nidhi Yadav were responsible for the conception, experiments, and writing and revising the manuscript.

CONFLICT OF INTERESTS

Declared none

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