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Review

Ehrlichiosis in Dogs: A Comprehensive Review about the Pathogen and Its Vectors with Emphasis on South and East Asian Countries

by
Muhammad Umair Aziz
1,
Sabir Hussain
1,
Baolin Song
1,
Hammad Nayyar Ghauri
2,
Jehan Zeb
1 and
Olivier Andre Sparagano
1,*
1
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR 999077, China
2
Department of Veterinary medicine, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan
*
Author to whom correspondence should be addressed.
Vet. Sci. 2023, 10(1), 21; https://doi.org/10.3390/vetsci10010021
Submission received: 5 December 2022 / Revised: 17 December 2022 / Accepted: 24 December 2022 / Published: 29 December 2022
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
Browse Figure
Review Reports Versions Notes

Abstract

:

Simple Summary

In dogs, ehrlichiosis is caused by three Ehrlichial species, namely Ehrlichia canis, E. ewingii, and E. chaffeensis; however, E. canis is the pathogen that most affects platelets, monocytes, and granulocytes. Globally, Rhipicephalus sanguineus is mainly responsible for vectoring the Ehrlichia species; however, Haemaphysalis longicornis is also involved in vectoring this species in east Asian countries. This disease causes acute, sub-clinical, and chronic clinical complications. There is no preferable age or sex for ehrlichiosis. The disease can be diagnosed by various methods including microscopy, indirect immunofluorescence test (IFAT), and polymerase chain reaction (PCR). The treatment of choice for ehrlichiosis includes doxycycline, rifampicin, and minocycline. Overall, this review describes the infection rate of Ehrlichia in dogs, the associated reported prevalence in east and south Asian countries, currently used therapy, and associated vectors responsible for the disease transmission as well as future perspectives.

Abstract

Ehrlichiosis in dogs is an emerging vector borne rickettsial zoonotic disease of worldwide distribution. In general, three Ehrlichial species (Ehrlichia canis, E. ewingii, and E. chaffeensis) are involved in infecting dogs. Among them, E. canis is the well-known etiological pathogen affecting platelets, monocytes, and granulocytes. Dogs act as a reservoir, while the main vector responsible for disease transmission is Rhipicephalus sanguineus. However, in east Asian countries, Haemaphysalis longicornis is considered the principal vector for disease transmission. This disease affects multiple organs and systems and has three clinical manifestations, including acute, subclinical, and chronic. Definitive diagnosis involves visualization of morulae on cytology, detection of antibodies through an indirect immunofluorescence test (IFAT), and DNA amplification by polymerase chain reaction (PCR). In canine ehrlichiosis, no predilection of age or sex is observed; however, Siberian Huskies and German Shepherds are more likely to develop severe clinical manifestations. Doxycycline, rifampicin, and minocycline are proven to be effective drugs against canine ehrlichiosis. This review is intended to describe a brief overview of Ehrlichia infection in dogs, its reported prevalence in east and south Asian countries, and the latest knowledge regarding chemotherapy and associated vectors responsible for the disease transmission. This manuscript also identifies the prevailing knowledge gaps which merit further attention by the scientific community.

1. Introduction

Ehrlichiosis is induced by a group of emerging rickettsial tick-borne pathogens of public importance that are Gram-negative obligate intracellular bacteria of the genus Ehrlichia, family Anaplasmataceae [1]. Ehrlichiosis in dogs is a significant vector-borne bacterial ailment spreading worldwide. It is also recognized as canine rickettsiosis, canine typhus, canine hemorrhagic fever, tropical canine pancytopenia, and tracker dog disease [2]. Numerous species of Ehrlichia are famous for infecting a wide range of animals. Among them, E. canis is the well-known etiological pathogen of canine ehrlichiosis affecting platelets, monocytes, and granulocytes [3,4]. Although E. chaffeensis is considered the main etiological agent of human monocytic ehrlichiosis (HME), it is also reported in canines [5]. A minimum of five different species of ticks (Amblyomma americanum, Haemaphysalis longicornis, Rhipicephalus sanguineus, Haemaphysalis yeni, and Dermacentor variabilis) have been identified as vectors transmitting clinical ehrlichiosis in dogs [6]. These disease-transmitting vectors become more potent during summer and spring seasons [7]. Rhipicephalus sanguineus (the brown tick of dogs) is generally considered the main vector responsible for canine ehrlichiosis [8,9]. In recent years, ehrlichiosis has been expanded to new regions which were thought to be disease free, such as northern China, temperate regions of the Indian sub-continent, and central and northern states of the USA [10].
Ticks are considered the second most prevalent hematophagous parasites after mosquitoes. Along with causing anemia, they also act as vectors for the transmission of many protozoan, bacterial, and viral diseases [11,12]. In recent years, ecological variations due to global warming, exponential increase in human population, deforestation, and frequent transport of pet animals from one continent to another have modified and enhanced the transmission patterns of all vector-borne pathogens around the globe [13]. In south and east Asia, regardless of the suitable climatic conditions for vectors and parasites and huge population of stray and pet dogs, scarce knowledge is available related to diagnosis, epidemiology, prevention, and control strategies associated with ehrlichiosis in dogs. However, with the expansion of a region’s economy and inculcation of foreign culture, the responsibilities of veterinarians have increased to devise control strategies about canine tick-borne ailments [14]. In less developed areas of east and south Asia, almost 75 percent of dogs are categorized as stray dogs, which further increases the risk of emergence of new tick-borne parasitic zoonoses [15].
Canine ehrlichiosis gained worldwide importance in the 1970s when a huge population of military German Shepherd dogs died during the Vietnam war [16]. Ehrlichia canis attacks cells of the immune system, particularly macrophages, leukocytes, and monocytes, developing a cytoplasmic membrane-bound cluster of bacteria termed morulae [17]. In the past, E.canis was not considered a zoonotic pathogen but recent studies have suggested its zoonotic significance in humans [18,19]. This disease affects multiple organs and systems and has three clinical presentations, including acute, subclinical, and chronic [20]. In the acute form, the main clinical symptoms in dogs are high fever, anorexia, lethargy, lymphadenomegaly, depression, epistaxis, splenomegaly, and petechial and ecchymotic skin hemorrhages. Ophthalmic lesions are also common and comprise chorioretinitis, papilledema, anterior uveitis, retinal hemorrhage, and occurrence of infiltrates at the retinal perivascular space [21]. The chronic form is more dangerous and characterized by anemia, paralysis, significant weakness, and death [20]. Due to several overlapping and non-specific clinical signs, diagnosis of the disease becomes challenging, and the need for alternative cutting edge molecular techniques is increasing [22]. This review is intended to describe a brief overview of Ehrlichia infection in dogs, its reported prevalence in east and south Asian countries, and the latest knowledge regarding chemotherapy and associated vectors responsible for the disease transmission. This manuscript also identifies the prevailing knowledge gaps which require the further attention of scientists.

2. Epidemiology

Ehrlichiosis is a disease of global importance, but it is more prevalent in sub-tropical and tropical regions. However, due to the chronic nature of the disease in some cases, accurate geographical distribution cannot be determined. The reason may be due to the fact that the clinical signs appear years after the first inoculation of the pathogen from ticks and after the canine species has traveled to non-endemic countries where this specific ailment might not be included in differential diagnostic lists by clinicians and scientists [23]. On the basis of different diagnostic methods, the prevalence in the south and east Asia ranges from 0.0% (South Korea) to 86.9% (India) [24,25]. The prevalence percentage of all Ehrlichia spp. related to canines in different countries of south and east Asia is presented in Table 1. Figure 1 depicts the prevalence of Ehrlichiosis across different regions.
In general, three Ehrlichia spp. (E. canis, E. ewingii, and E. chaffeensis) are involved in infecting dogs [66]. However, in Japan, variations among tick and Ehrlichia spp. are more evident. Instead of R. sanguineus, Haemaphysalis longicornis is the most commonly found tick species responsible for disease spread [67]. In recent times, a novel Ehrlichia species was found in Ixodes ovatus ticks, which showed phylogenetically close relationship with E. chaffeensis [68]. Similarly, Rhipicephalus sanguineus is rarely found in Korea. Instead, the most common tick species found in Korean dogs are H. longicornis and Haemaphysalis flava [5]. H. longicornis also possesses zoonotic significance because it has been found in close association with animals and humans [57]. Although Amblyomma americanum is the chief vector involved in E. chaffeensis infection, Haemaphysalis yeni, testudinarium, Ixodes ricinus, and H. flava have also been isolated as reservoirs [69,70,71].
Since its discovery, human monocytotropic ehrlichiosis (HME) has grown to be the most common life-threatening tick-borne disease. As the number of animal reservoirs and tick vectors have increased and people have increasingly settled in areas with high reservoir and tick populations, ehrlichiosis is being diagnosed as the primary cause of human diseases. The causative agent of HME, Ehrlichia chaffeensis, is a developing zoonosis that can have a variety of clinical presentations, from a mild febrile sickness to a fulminant disease marked by multiorgan system failure. Headache, fever, leukopenia, thrombocytopenia, and increased liver enzymes are among the clinical symptoms of human monocytic ehrlichiosis (HME). The majority of patients need medical assistance during the first 4 days of sickness, with symptoms often appearing 9 days on average after a tick bite. The majority of HME reports involve neurological symptoms [72].

3. Risk Factors Associated with Canine Ehrlichiosis

All dog breeds are susceptible to canine monocytic ehrlichiosis (CME). Nevertheless, because Siberian Huskies and German Shepherds are more prone to exhibit severe clinical symptoms, infection in these breeds frequently has the worst prognosis [72,73]. This was demonstrated experimentally by infecting German Shepherd and Beagle dogs with E. canis and seeing that the intensity of the cell-mediated immune response in the German Shepherd breed was lower than that of the Beagle breed dogs [72,73,74]. It seems that there is no predisposition of sex in disease occurrence. Although some published literature has detected increased seroreactivity in males, this can be explained by a higher chance of contact with tick species than females because of behavioral features [75]. There is no strong evidence of high disease prevalence in older dogs as well. However, some epidemiological studies show that seropositivity rates were higher in older dogs [50,76]. These results may be due to the higher likelihood of exposure to the Ehrlichia pathogen as the dog becomes older. Dogs living outdoors are more prone to have ehrlichiosis compared with pet dogs living indoors. Moreover, dogs living in non-sanitized enclosures with tick infestations are at risk of getting E. canis infection. Regular use of ectoparasiticidal drugs also decrease the risk of ehrlichiosis in dogs [77]. Moreover, environmental factors also play a major role in disease prevalence because high temperature and low humidity favors the growth of vectors, so animals living in those circumstances are at greater risk [78].Ticks spreading the disease are mentioning in Table 2.

4. Transmission Cycle

Brown dog tick (Rhipicephalus sanguineus) carries the pathogen from infected dog through blood meal during the acute phase of disease. After the blood meal, E. canis resides in the salivary glands and midgut of the carrier tick and it then spreads the pathogen to another healthy dog via its salivary glands during subsequent feeding [81]. Transstadial transmission is well-established for this pathogen in which the larval stage of tick becomes infected with E. canis, which can pass the bacteria to the next two stages (nymph and adult) and spread the pathogen during blood meals [82,83]. It has been observed that brown dog tick starts transferring the rickettsial pathogens within three hours of its attachment to a host [83]. If the Rhipicephalus sanguineus is transferred to a cold or temperate climate, due to the shifting of hosts, it can still remain active under such man-made protected kennel environments [84,85]. Moreover, enclosures of wild animals, abandoned houses, and kennel environments provide a perfect atmosphere for its reproduction. Under these suitable environmental conditions, only a single female tick was enough to infect and reproduce many subadults [86]. During the chronic or subclinical phase of the disease, the dog seems healthy but still acts as a carrier for this rickettsial pathogen. The only tick that becomes engorged during the acute phase can infect another healthy host. Moreover, this tick can spread the bacteria even after 155 days of its detachment [87]. Many studies have suggested that transovarial spread of the pathogen also occurs in Ixodid ticks and they maintain the bacteria through many generations in nature [88,89]. However, in a recent study, no proof of transovarial spread was found [90].

5. Pathogenicity

Unlike many Gram-negative bacterial pathogens, peptidoglycan and lipopolysaccharide are absent in the cell wall of this bacterium which may help the bacteria in resisting the host’s immune response. The cell wall of E. canis becomes very flexible due to the absence of these two materials, which in turn facilitates the pathogen in avoiding antibody attack from its host immune system. Other characteristic feature of this rickettsial organism is the lack of complex inner structures, which permits the production of sugars. The main energy source of this bacterium are amino acids [91]. The incubation period of Ehrlichia ranges from 8–20 days. This period is sequentially followed by subclinical, acute, or in some cases chronic form.
Pilli are absent in Ehrlichia so the outer membrane of this infectious agent helps in the attachment with the host cell. Once the pathogen enters the host cell and starts infection, it forms membrane-bound partitions (endosomes) and maintains its distinctive cytoplasmic shape. The main target of E. canis are mononuclear phagocytic cells. Monocytes are the most common cells to be infected both in canine and human hosts. In addition, Ehrlichia also attacks the other immune cells such as metamyelocytes, lymphocytes, and promyelocytes. In general, it is assumed that inside the cells only mononuclear phagocytic cells are able to uphold the productive pathogen [92]. On average, a single infected monocyte contains one to two morulae. The endosomal membrane formed by Ehrlichia protects the pathogen from the host and it multiplies within this apartment. The exact mechanism of their survival is still unclear but consequently, the pathogen may survive by modulating the host defense system [93]. In one study, researchers identified two paralogous proteins responsible for immune evasion, which may be due to the presence of poly (G-C) tracts in one of the proteins, suggesting that they have a role in facilitating chronic persistent infections and can help in phase deviation [91].
After infecting the monocytes, E. canis spreads to the whole lymphatic system including the liver and spleen, where it triggers the abnormal fast growth of cells and the increased size of these organs, described as hyperplasia. Further cell division and replication leads to bacteremia and eventually results in hemolysis. At this stage, severe clinical manifestations, such as high fever, anemia, and thrombocytopenia, can be observed [50]. Dogs suffering from persistent infection develop a more lethal form of chronic disease where the pathogen attacks the bone marrow and destroys the immune system. As a result, other opportunistic infectious agents further aggravate the situation. Severe thrombocytopenia leads to massive hemorrhages and death [91].

6. Clinical Signs

Clinical presentation due to ehrlichial infection can be varied and depends on many factors, such as the status of the immune system of the dog, virulence of the strain, and existence of co-infections with other tick/flea-borne diseases. Among all other members of the Anaplasmataceae family, E. canis appears to cause more intense clinical abnormalities [94,95,96]. In dogs, three ehrlichial species, namely E. canis, E. ewingii, and E. chaffeensis, can cause clinical disease [1,3]. The principal host cell targets for E. canis and E. chaffeensis are agranulocytes, while E. ewingii mainly targets the granulocytic white blood cells [2]. These pathogens can induce both clinical and subclinical complications. Clinical signs induced by ehrlichial species are often non-specific and overlapping. The disease can be acute or mild; however, in many cases, the animal becomes a carrier for an extended period of time without presenting any clinical manifestations. Typically, the incubation period for all ehrlichial species ranges from one to three weeks, and results in three possible disease presentations which may be categorized as acute, chronic, and subclinical [97]. The acute phase may last for 2 to 4 weeks and if the animal survives, the signs vanish even without chemotherapeutic treatment. However, some dogs become subclinical carriers after improvement and may become an important source of infection for months and years. In this phase, the animal apparently looks normal and healthy and does not present any clinically visible signs but upon hematological testing, mild thrombocytopenia can be detected [98]. Not all but some subclinically infected dogs may proceed to the chronic stage, which is the most fatal form of the disease, and which cannot be differentiated from the acute phase in clinical settings because most of the clinical manifestations are non-specific. The chronic form is also known as the myelosuppressive form in which it is difficult to distinguish it from acute bone marrow aspiration and complete blood count tests are necessary. Alternatively, hypoplasia of bone marrow and severe pancytopenia will confirm the presence of the chronic phase [99]. The possible factors that cause some dogs to enter the chronic phase are still unclear.
In naturally infected dogs, the common clinical findings are fever, pale mucosa due to anemia, lymphadenomegaly, bleeding disorders, hepatomegaly, lethargy, petechial and ecchymotic hemorrhages, vasculitis, and extended bleeding period during estrus [100,101,102]. Other less common signs of ehrlichiosis have also been defined and include diarrhea, exercise intolerance, neonatal death or abortion, vomiting, and mucopurulent or serous nasal and ocular discharge. Some old studies have mentioned polyarthritis and lameness as a sign of canine ehrlichiosis [103], but it is believed that this manifestation only appears in cases of co-infections. On physical examination, you may observe tick infestation particularly during the acute phase. In addition, other signs like ataxia, vestibular dysfunction and seizures, and chronic or myelosuppressive form also reveal stomatitis, scrotal or hind limb edema, jaundice, glossitis, and pyoderma [104]. Bleeding tendencies are also more frequent and severe in the chronic form of CME [102].

7. Clinical Pathology

Hematological abnormalities are variable and overlapping. However, severe drop in platelet count or thrombocytopenia is the principal abnormality observed in canine ehrlichiosis. This hematological finding is consistent in almost 80% of the animals, irrespective of the stage of the ailment. However, normal platelet count may not be the only reason to rule out ehrlichiosis [105,106]. In a retrospective study, decreases in total red blood cell count, pack cell volume (PCV), and platelet count while noticeable increases in basophil count were observed. Moreover, blood urea nitrogen (BUN) and creatinine levels were more elevated than normal [107]. Anemia is mostly non-regenerative along with lymphopenia, monocytosis, thrombocytopathy, hyperproteinemia, hypergammaglobulinemia, hypoalbuminemia, and hyperglobulinemia, which are some additional irregularities [108,109,110]. Values of neutrophils are inconsistent and both neutrophilia and neutropenia have been detected based on the phase of the severity. In the chronic form, aplastic pancytopenia, granular lymphocytosis, mild elevation in liver enzymes, and renal azotemia were found. In regions where this disease is endemic, CME should be the top differential in dogs having persistent lymphocytosis [111,112].
Histopathological and gross abnormalities in experimentally infected dogs include edema of the subcutaneous layer, ascites, anemia, jaundice, and emaciation. Cuffing of the lymphatic fluid in the cerebellum and brain is occasionally seen. Lungs of infected animals display vasculitis and interstitial pneumonia. Additionally, a flabby heart and whole heart dilatation can also be found. Grossly, the most frequent signs include apparent splenomegaly, multifocal lymph node necrosis, and widespread lymadenopathy [113].

8. Diagnosis

8.1. Microcopy

In blood smears, detection of ehrlichial organisms in the form of morulae is very rare. It is noticeable only in 4–6% of cases. The higher sensitivity of this method can be achieved by using a buffy coat smear [114,115]. Maximum detection percentage (50%) of morulae can be achieved by an expert cytologist that observes many microscopic fields using fluid from lymph nodes [116]. In the acute form of canine ehrlichiosis, the presence of E. canis morulae in mononuclear leukocytes using buffy coat, spleen, cerebrospinal fluid, and bone marrow provides a definitive diagnosis [117,118]. In one study, they measured the percentage of morulae detection in naturally infected dogs using lymph nodes, buffy coat, and their combination and found a 61%, 66%, and 74% detection rate, respectively [119]. Cytology is considered a laborious procedure having low diagnostic sensitivity but in acute cases it can provide earlier diagnosis even before serology. This method can also be helpful in documenting mix infections [92]. Bone marrow cytology is also used to differentiate myelosuppressive and non-myelosuppressive canine ehrlichiosis as well [12]. One of the limitations of microscopy is that it is extremely insensitive in the chronic and subclinical phases and unable to differentiate ehrlichial species. Moreover, it requires a lot of expertise to differentiate between other extraneous tissue structures and morulae [22].

8.2. Serology

Immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) can both be used for the diagnosis of ehrlichiosis [120,121]. Specific apparatus and technical manpower are required to run these tests. One of the benefits of using serological tests for the detection of infectious pathogens is that they can quantify the antibody titer and variations over time. Consequently, it gives an idea about the stage and intensity of infection. Quantitative serological methods have a high sensitivity and specificity rate as compared with rapid diagnostic tests [2]. The perseverance of moving antibodies can also have an advantage especially during the chronic phase of canine monocytic ehrlichiosis (CME) when the quantity of active pathogen in blood is too low to be measured through PCR or the pathogen is confiscated in tissues not normally submitted to run PCR [100,122]. Positive ELISA or IFAT only denote a past or present infection and does not indicate the current disease condition. You can get a positive result on the basis of antibody titer even when the infection is resolved in the past because antibodies may persist in the body for several months or even years [123]. Regardless of carrying an active infection, an animal can be serologically negative especially during the early stages of the ailment or during the incubation period. In ehrlichiosis, normally antibody synthesis does not start before 12 to 14 days after infection [124]. We propose that doubted cases must be accessed based on two to three serological tests performed within two to three weeks. Through this approach, we can check the trend of antibody titer (increasing, decreasing, or constant) and guess the present status of the malady. In a study, they mentioned the 4-fold growth of IgG as proof of a current infection [120]. Generally, it is assumed that there is no cross-reaction present between Ehrlichia and other Anaplasmataceae members. However, a possible such reaction has been defined between A. phagocytophilum and E. canis, mainly when the quantity of one pathogen was very high [125].

8.3. Molecular

PCR is very valuable in identifying these canine infectious ailments for many reasons. First, it can detect a minute amount of DNA with high precision. Secondly, instead of indicating past infections, it provides strong and clear evidence about the active ongoing disease. Early infections, which otherwise cannot be diagnosed through serology, can easily be analyzed through PCR. This test (real-time PCR) allows the quantitative evaluation of rickettsial pathogens. Multiplex PCR has the ability to discover co-infections as well [110,126]. Moreover, to evaluate persistently infected (subclinical form) carrier animals and for evaluating the efficacy of different chemotherapeutic trials, PCR is mandatory [127]. In past, genus-specific disulfide bond formation protein (dsb) gene were targeted for diagnosis [128]. Regarding E. canis, many molecular assays have been established targeting species-specific genes like p30 and 16S rRNA genes. p30 is considered more specific than 16SrRNA gene based on nested PCR. However, (IFAT) is considered the gold standard test by OIE for the diagnosis of Ehrlichia [129].

9. Treatment

Among antibiotics, tetracyclines were the first group to be used successfully against CME [16]. Doxycycline (semi-synthetic tetracycline) is approved experimentally both in vitro and in naturally infected dogs as the first-line treatment of choice. Ideal dose rate and duration of doxycycline is 10 mg/kg once (per os) daily or 5 mg/kg twice (orally) daily minimum for four weeks. This protocol warrants a satisfactory response in most of the cases [97,130]. In some studies, it has been approved that if we reduced the duration of treatment with doxycycline, complete elimination of E. canis became impossible and dogs played their role as carriers without displaying any clinical manifestations [131,132]. Thus, a complete four-week treatment protocol is recommended. As opposed to achieving clinical improvement, systematic removal of infection is difficult to accomplish, especially in naturally diseased dogs. Therefore, rather than post-treatment seronegativity, PCR negative results should be the target of clinicians [133].
In contrast to other tetracyclines, doxycycline is considered safe and does not cause discoloration of enamel. Vomiting is the second most common side effect of these antibiotics; this can be minimized by dividing the dose into two halves or by giving it after feeding. Prolonged use of doxycycline can damage hepatocytes, so if the liver enzymes increase, treatment must be paused [124,134]. The efficacy of minocycline has recently been evaluated for the chemotherapy of CME and it has shown a similar efficacy to doxycycline by eliminating the infection from all five dogs [135]. However, due to the very small sample size, it is suggested that more comprehensive studies should be conducted to declare minocycline as the first line of drug against CME [136]. Historically, chloramphenicol has also been used for treating ehrlichiosis in young dogs (less than 1 year of age). It is not recommended to administer chloramphenicol when doxycycline is accessible. In the past, imidocarb dipropionate was also considered effective against canine ehrlichiosis but more recent studies have revealed that it was only effective during co-infections and not against E. canis [137,138]. Rifampicin has been potentially useful in experimentally induced in vitro studies [139]. Further studies concluded that rifampicin can only decrease the intensity of clinical manifestations but could not eliminate the pathogen thoroughly from cells [140].

10. Post-Treatment Monitoring

Post-treatment supervision is chiefly vital in ehrlichiosis. Dissimilar to the myelosuppressive chronic form where treatment is largely ineffective, fast recovery (within 24–48 h) in the acute form is observed after the first dose, whereas blood cell abnormalities can be resolved within one to three weeks [131,141]. Another essential fact which we should keep in mind is that retrieval of hematological and clinical irregularities may surpass the exclusion of E. canis, so, the complete four-week treatment regime should be followed even when animal apparently looks normal. Recurrence of thrombocytopenia after the termination of doxycycline therapy shows failure of chemotherapy [142]. Constant presence of hyperglobulinemia even after 6 to 9 months of treatment stipulates coexisting infections or unsuccessful treatment. Quantitative serological tests cannot be used as a monitoring tool after treatment because values of IgG antibodies fluctuate randomly and remain there for months or years [143]. Therefore, from a clinical perspective, molecular detection (PCR) of bacteria is a reliable tool to declare clearance [144].

11. Prevention and Control

Even after the complete recovery from natural infection, dogs do not develop life-long immunity and there are still chances of re-infection [131]. That is why vector control by spraying suitable acaricides at regular intervals, by careful removal of ticks manually, or by monitoring of environmental factors related to tick growth, are fundamental control procedures in handling ehrlichiosis [145]. Recently, a study mentioned that transmission of E. canis may start after three to eight hours of tick infestation [144]. Commercially available ectoparasitic drugs such as pyrethroids (tetramethrin, permethrin, flumethrin, deltamethrin), phenylpyrazoles (fipronil, pyriprol), isoxazolines (sarolaner, fluralaner, afoxolaner), and amitraz have shown good efficacy regarding the killing of ticks involved in disease spread. However, owners must be educated about the development of resistance against these drugs and should encourage alternative use of different acaricides [144,145]. In regions where the disease is endemic, prophylactic use of doxycycline especially during summer and spring (tick season) can lower the risk of infection [145]; however, the probability of resistance increases with this practice. Dogs traveling from endemic areas must be screened for CME before entering.

12. Future Perspectives and Recommendations

The above discussion shows that ehrlichiosis in dogs is a vector-borne rickettsial ailment of zoonotic importance spreading globally. It is necessary to pay attention to canine ehrlichiosis and further research should focus on the following areas:
(1)
Molecular epidemiological surveys to investigate other tick species responsible for disease spread in different regions of the world for devising better control measures.
(2)
The role of other wild carnivores should be explored as a reservoir for this bacterium.
(3)
Further studies on finding the exact mechanism of immune envision.
(4)
The zoonotic potential of some ehrlichial species such as E. canis is not fully discovered yet, so health-based studies should be conducted.
(5)
Further genome-based studies to find pathogenic pathways/proteins for vaccine development.
(6)
Up to now, only one antibiotic class is mainly effective, so studies on finding new antibiotics are important.
(7)
In subtropical and tropical areas with an abundance of vectors, infection by two or more vector-borne pathogens is typical. Co-infections may accelerate the progression of a disease, changing the clinical signs and symptoms that are usually connected to a single infection. If the practitioner neglects to suspect, record, and treat each concurrent infection, these factors confound diagnosis, treatment, and can negatively affect prognosis. Canine ehrlichiosis has often been diagnosed with anaplasmosis or babesiosis in dogs. Thus, this co-infection halts the diagnosis of the exact etiological agent participating in a certain pathology, so pathophysiology and clinical presentation during co-infections need to be explored.

13. Conclusions

This review summarizes the current literature available on prevalence, geographical distribution, pathogenesis, epidemiology, and treatment as well as diagnostic methods of ehrlichiosis in dogs with special emphasis on east and south Asia. Data accessibility and availability regarding canine ehrlichiosis varies greatly between different countries of south and east Asia. Some countries, such as China and India, have profound availability of data about Ehrlichia; however, in Sri Lanka, Bhutan, Afghanistan, and North Korea, data are unavailable. Much of the literature reviewed about east Asian countries is very old, indicating the need for new research. In short, it is concluded that further research is needed with special emphasis on novel diagnostic tools, pathogenesis, epidemiology, disease transmission, and zoonoses regarding ehrlichiosis to explore a potential era for future studies.

Author Contributions

M.U.A., S.H. and B.S. conceived the study, drafted the manuscript, and revised the manuscript. H.N.G., J.Z. and O.A.S. provided intellectual inputs, and O.A.S. critically revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

Olivier Andre Sparagano is a principal investigator of an internal research fund of the Department of Infectious Diseases and Public Health of the City University of Hong Kong (Project number 9380108).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data is contained within the article.

Conflicts of Interest

The authors declare that they have no competing interests, and this study was conducted in the absence of any commercial or financial relationship.

References

  1. Jafarbekloo, A.; Bakhshi, H.; Faghihi, F.; Telmadarraiy, Z. Molecular Detection of Anaplasma and Ehrlichia Infection in Ticks in Borderline of Iran-Afghanistan. J. Biomed. Sci. Eng. 2014, 7, 919–926. [Google Scholar] [CrossRef] [Green Version]
  2. Beall, M.J.; Alleman, A.R.; Breitschwerdt, E.B.; Cohn, L.A.; Couto, C.G.; Dryden, M.W.; Guptill, L.C.; Iazbik, C.; Kania, S.A.; Lathan, P.; et al. Seroprevalence of Ehrlichia Canis, Ehrlichia Chaffeensis and Ehrlichia Ewingii in Dogs in North America. Parasit Vectors 2012, 5, 29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Stiles, J. Canine Rickettsial Infections. Vet. Clin. N. Am.-Small Anim. Pract. 2000, 30, 1135–1149. [Google Scholar] [CrossRef] [PubMed]
  4. Lorsirigool, A.; Pumipuntu, N. A Retrospective Study of Dogs Infected with Ehrlichia Canis from 2017–2019 in the Thonburi Area of Bangkok Province, Thailand. Int. J. Vet. Sci. 2020, 9, 578–580. [Google Scholar] [CrossRef]
  5. Yu, D.H.; Li, Y.H.; Yoon, J.S.; Lee, J.H.; Lee, M.J.; Yu, I.J.; Chae, J.S.; Park, J.H. Ehrlichia Chaffeensis Infection in Dogs in South Korea. Vector-Borne Zoonotic Dis. 2008, 8, 355–357. [Google Scholar] [CrossRef] [Green Version]
  6. Keith, C.; Fuqua, C.; Lively, C.; Wade, M.J. Microbial Community Ecology of Tick-Borne Human Pathogens. In Disease Ecology: Community Structure and Pathogen Dynamics; Oxford University Press: Oxford, UK, 2007. [Google Scholar]
  7. Neer, T.M.; Harrus, S. Canine monocytotropic ehrlichiosis and neorickettsiosis. E. Canis E. Chaffeensis E. Rumin. N. Sennetsu 2006, 203–216. [Google Scholar]
  8. Groves, M.G.; Dennis, G.L.; Amyx, H.L.; Huxsoll, D.L. Transmission of Ehrlichia Canis to Dogs by Ticks (Rhipicephalus Sanguineus). Am. J. Vet. Res. 1975, 36, 937–940. [Google Scholar]
  9. Aguiar, D.M.; Cavalcante, G.T.; Pinter, A.; Gennari, S.M.; Camargo, L.M.A.; Labruna, M.B. Prevalence of Ehrlichia Canis (Rickettsiales: Anaplasmataceae) in Dogs and Rhipicephalus Sanguineus (Acari: Ixodidae) Ticks from Brazil. J. Med. Entomol. 2007, 44, 126–132. [Google Scholar] [CrossRef]
  10. Sainz, Á.; Roura, X.; Miró, G.; Estrada-Peña, A.; Kohn, B.; Harrus, S.; Solano-Gallego, L. Guideline for Veterinary Practitioners on Canine Ehrlichiosis and Anaplasmosis in Europe. Parasites Vectors 2015, 8, 75. [Google Scholar] [CrossRef] [Green Version]
  11. de la Fuente, J.; Estrada-Pena, A.; Venzal, J.M.; Kocan, K.M.; Sonenshine, D.E. Overview: Ticks as Vectors of Pathogens That Cause Disease in Humans and Animals. Front. Biosci. 2008, 13, 6938–6946. [Google Scholar] [CrossRef] [Green Version]
  12. Otranto, D.; Dantas-Torres, F.; Giannelli, A.; Latrofa, M.; Cascio, A.; Cazzin, S.; Ravagnan, S.; Montarsi, F.; Zanzani, S.; Manfredi, M.; et al. Ticks Infesting Humans in Italy and Associated Pathogens. Parasites Vectors 2014, 7, 328. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Dantas-Torres, F. Climate Change, Biodiversity, Ticks and Tick-Borne Diseases: The Butterfly Effect. Int. J. Parasitol. Parasites Wildl. 2015, 4, 452–461. [Google Scholar] [CrossRef] [PubMed]
  14. Megat Abd Rani, P.A.; Irwin, P.J.; Gatne, M.; Coleman, G.T.; Traub, R.J. Canine Vector-Borne Diseases in India: A Review of the Literature and Identification of Existing Knowledge Gaps. Parasites Vectors 2010, 3, 28. [Google Scholar] [CrossRef] [Green Version]
  15. Traub, R.J.; Irwin, P.; Dantas-Torres, F.; Tort, G.P.; Labarthe, N.V.; Inpankaew, T.; Gatne, M.; Linh, B.K.; Schwan, V.; Watanabe, M. Toward the Formation of a Companion Animal Parasite Council for the Tropics (CAPCT). Parasites Vectors 2015, 8, 1–5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Amyx, H.L.; Huxsoll, D.L.; Zeiler, D.C.; Hildebrandt, P.K. Therapeutic and Prophylactic Value of Tetracycline in Dogs Infected with the Agent of Tropical Canine Pancytopenia. J. Am. Vet. Med. Assoc. 1971, 159, 1428–1432. [Google Scholar]
  17. Mylonakis, M.E.; Theodorou, K.N. Canine Monocytic Ehrlichiosis: An Update on Diagnosis and Treatment. Acta Vet. 2017, 67, 299–317. [Google Scholar] [CrossRef] [Green Version]
  18. Perez, M.; Bodor, M.; Zhang, C.; Xiong, Q.; Rikihisa, Y. Human Infection with Ehrlichia Canis Accompanied by Clinical Signs in Venezuela. Ann. N. Y. Acad. Sci. 2006, 1078, 110–117. [Google Scholar] [CrossRef]
  19. Andrić, B. Diagnostic Evaluation of Ehrlichia Canis Human Infections. Open J. Med. Microbiol. 2014, 4, 132–139. [Google Scholar] [CrossRef] [Green Version]
  20. Harrus, S.; Waner, T. Diagnosis of Canine Monocytotropic Ehrlichiosis (Ehrlichia Canis): An Overview. Vet. J. 2011, 187, 292–296. [Google Scholar] [CrossRef]
  21. Komnenou, A.A.; Mylonakis, M.E.; Kouti, V.; Tendoma, L.; Leontides, L.; Skountzou, E.; Dessiris, A.; Koutinas, A.F.; Ofri, R. Ocular Manifestations of Natural Canine Monocytic Ehrlichiosis (Ehrlichia Canis): A Retrospective Study of 90 Cases. Vet. Ophthalmol. 2007, 10, 137–142. [Google Scholar] [CrossRef]
  22. Bai, L.; Goel, P.; Jhambh, R.; Kumar, P.; Joshi, V.G. Molecular Prevalence and Haemato-Biochemical Profile of Canine Monocytic Ehrlichiosis in Dogs in and around Hisar, Haryana, India. J. Parasit. Dis. 2017, 41, 647–654. [Google Scholar] [CrossRef] [PubMed]
  23. Neer, T.M. Canine Monocytic and Granulocytic Ehrlichiosis, 2nd ed.; WB Saunders: Philadelphia, PA, USA, 1998; pp. 139–147. [Google Scholar]
  24. Kottadamane, M.R.; Dhaliwal, P.S.; das Singla, L.; Bansal, B.K.; Uppal, S.K. Clinical and Hematobiochemical Response in Canine Monocytic Ehrlichiosis Seropositive Dogs of Punjab. Vet. World 2017, 10, 255–261. [Google Scholar] [CrossRef] [PubMed]
  25. Truong, A.-T.; Noh, J.; Park, Y.; Seo, H.-J.; Kim, K.-H.; Min, S.; Lim, J.; Yoo, M.-S.; Kim, H.-C.; Klein, T.A. Molecular Detection and Phylogeny of Tick-Borne Pathogens in Ticks Collected from Dogs in the Republic of Korea. Pathogens 2021, 10, 613. [Google Scholar] [CrossRef] [PubMed]
  26. Malik, M.I.; Qamar, M.; Ain, Q.; Hussain, M.F.; Dahmani, M.; Ayaz, M.; Mahmood, A.K.; Davoust, B.; Shaikh, R.S.; Iqbal, F. Molecular Detection of Ehrlichia Canis in Dogs from Three Districts in Punjab (Pakistan). Vet. Med. Sci. 2018, 4, 126–132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Iatta, R.; Sazmand, A.; Nguyen, V.L.; Nemati, F.; Ayaz, M.M.; Bahiraei, Z.; Zafari, S.; Giannico, A.; Greco, G.; Dantas-Torres, F.; et al. Vector-Borne Pathogens in Dogs of Different Regions of Iran and Pakistan. Parasitol. Res. 2021, 120, 4219–4228. [Google Scholar] [CrossRef]
  28. Kalaivanan, M.; Saravanan, S.; Palanivel, K.M.; Ponnudurai, G.; Veterinary, T.N. Identification of ehrlichia canis by pcr with phylogenetic analysis in dogs from south india. Haryana Vet. 2020, 59, 79–82. [Google Scholar]
  29. Behera, S.K.; Dimri, U.; Banerjee, P.; Garg, R.; Dandapat, S.; Sharma, B. Molecular Detection and Assessment of Hemato-Biochemistry, Oxidant/Antioxidant Status in Natural Canine Monocytic Ehrlichiosis Cases from Northern India. Proc. Natl. Acad. Sci. India Sect. B-Biol. Sci. 2017, 87, 361–368. [Google Scholar] [CrossRef]
  30. Manoj, R.R.S.; Iatta, R.; Latrofa, M.S.; Capozzi, L.; Raman, M.; Colella, V.; Otranto, D. Canine Vector-Borne Pathogens from Dogs and Ticks from Tamil Nadu, India. Acta Trop. 2020, 203, 105308. [Google Scholar] [CrossRef]
  31. Milanjeet; Singh, H.; Singh, N.K.; Singh, N.D.; Singh, C.; Rath, S.S. Molecular Prevalence and Risk Factors for the Occurrence of Canine Monocytic Ehrlichiosis. Vet. Med. (Praha) 2014, 59, 129–136. [Google Scholar] [CrossRef] [Green Version]
  32. Lakshmanan, B.; John, L.; Gomathinayagam, S.; Dhinakarraj, G. Molecular Detection of Ehrlichia Canis from Blood of Naturally Infected Dogs in India. Vet. Arh. 2007, 77, 307–312. [Google Scholar]
  33. das Singla, L.; Sumbria, D.; Mandhotra, A.; Bal, M.S.; Kaur, P. Critical Analysis of Vector-Borne Infections in Dogs: Babesia Vogeli, Babesia Gibsoni, Ehrlichia Canis and Hepatozoon Canis in Punjab, India. Acta Parasitol. 2016, 61, 697–706. [Google Scholar] [CrossRef] [PubMed]
  34. Singla, L.D.; Singh, H.; Kaur, P.; Singh, N.D.; Singh, N.K.; Juyal, P.D. Serodetection of Ehrlichia Canis Infection in Dogs from Ludhiana District of Punjab, India. J. Parasit. Dis. 2011, 35, 195–198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Kukreti, K.; Das, M.K.; Rastogi, A.K.; Dubey, R.; Pandey, L.K.; Sharma, P. Prevalence of Canine Monocytic Ehrlichiosis in Canine Population across India. Arch. Razi Inst. 2018, 73, 87–93. [Google Scholar] [CrossRef]
  36. Mittal, M.; Kundu, K.; Chakravarti, S.; Mohapatra, J.K.; Nehra, K.; Sinha, V.K.; Sanjeeth, B.S.; Churamani, C.P.; Kumar, A. Canine Monocytic Ehrlichiosis among Working Dogs of Organised Kennels in India: A Comprehensive Analyses of Clinico-Pathology, Serological and Molecular Epidemiological Approach. Prev. Vet. Med. 2017, 147, 26–33. [Google Scholar] [CrossRef]
  37. Wise, A.E.; Tarlinton, R.E. Seroprevalence of Vectorborne Diseases in Free-Roaming Dogs in Goa, India. Vet. Rec. 2012, 170, 76. [Google Scholar] [CrossRef]
  38. Díaz-Regañón, D.; Agulla, B.; Piya, B.; Fernández-Ruiz, N.; Villaescusa, A.; García-Sancho, M.; Rodríguez-Franco, F.; Sainz, Á. Stray Dogs in Nepal Have High Prevalence of Vector-Borne Pathogens: A Molecular Survey. Parasites Vectors 2020, 13, 1–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  39. Phuyal, S.; Jha, V.C.; Subedi, M. Prevalence of Blood Parasites in Dogs of Kathmandu Valley. Nepal. Vet. J. 2017, 34, 107–112. [Google Scholar] [CrossRef] [Green Version]
  40. Talukder, B.M.H.; Matsuu, A.; Iguchi, A.; Roy, B.C.; Nishii, N.; Hikasa, Y. PCR-Based Survey of Vector-Borne Pathogens in Dogs In. J. Bangladesh. Agril. Univ. 2012, 10, 249–253. [Google Scholar] [CrossRef] [Green Version]
  41. Luo, H.; Lan, Y.; Gan, P.; Zhou, W.; Wang, M.; Hu, B.; Zhang, Z.; Bai, Y.; Li, K. Molecular Identification and Prevalence of Ehrlichia Canis and Rhipicephalus Sanguineus (Acari: Ixodidae) Infecting Pet Dogs in Wenzhou, China. Pak. J. Zool. 2021, 53, 2129. [Google Scholar] [CrossRef]
  42. Mengfan, Q.; Lixia, W.; Ying, L.; Yan, R.; Kuojun, C.; Jinsheng, Z.; Zaichao, Z.; Weiwei, Y.; Yelong, P.; Xuepeng, C.; et al. Molecular Detection and Genetic Variability of Ehrlichia Canis in Pet Dogs in Xinjiang, China. Vet. World 2020, 13, 916–922. [Google Scholar] [CrossRef] [PubMed]
  43. Xu, D.; Zhang, J.; Shi, Z.; Song, C.; Zheng, X.; Zhang, Y.; Hao, Y.; Dong, H.; Wei, L.; El-Mahallawy, H.S.; et al. Molecular Detection of Vector-Borne Agents in Dogs from Ten Provinces of China. Parasites Vectors 2015, 8, 1–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Zhang, J.; Liu, Q.; Wang, D.; Li, W.; Beugnet, F.; Zhou, J. Epidemiological Survey of Ticks and Tick-Borne Pathogens in Pet Dogs in South-Eastern China. Parasite 2017, 24, 35. [Google Scholar] [CrossRef] [PubMed]
  45. Xia, Z.; Yu, D.; Mao, J.; Zhang, Z.; Yu, J. The Occurrence of Dirofilaria Immitis, Borrelia Burgdorferi, Ehrlichia Canis and Anaplasma Phagocytophium in Dogs in China. J. Helminthol. 2012, 86, 185–189. [Google Scholar] [CrossRef] [PubMed]
  46. Chen, Z.; Liu, Q.; Liu, J.Q.; Xu, B.L.; Lv, S.; Xia, S.; Zhou, X.N. Tick-Borne Pathogens and Associated Co-Infections in Ticks Collected from Domestic Animals in Central China. Parasites Vectors 2014, 7, 1–8. [Google Scholar] [CrossRef] [Green Version]
  47. Yu, P.F.; Niu, Q.L.; Liu, Z.J.; Yang, J.F.; Chen, Z.; Guan, G.Q.; Liu, G.Y.; Luo, J.X.; Yin, H. Molecular Epidemiological Surveillance to Assess Emergence and Re-Emergence of Tick-Borne Infections in Tick Samples from China Evaluated by Nested PCRs. Acta Trop. 2016, 158, 181–188. [Google Scholar] [CrossRef]
  48. Colella, V.; Nguyen, V.L.; Tan, D.Y.; Lu, N.; Fang, F.; Zhijuan, Y.; Wang, J.; Liu, X.; Chen, X.; Dong, J.; et al. Zoonotic Vectorborne Pathogens and Ectoparasites of Dogs and Cats in Eastern and Southeast Asia. Emerg. Infect. Dis. 2020, 26, 1221–1233. [Google Scholar] [CrossRef]
  49. Zheng, W.; Liu, M.; Moumouni, P.F.A.; Liu, X.; Efstratiou, A.; Liu, Z.; Liu, Y.; Tao, H.; Guo, H.; Wang, G.; et al. First Molecular Detection of Tick-Borne Pathogens in Dogs from Jiangxi, China. J. Vet. Med. Sci. 2017, 79, 248–254. [Google Scholar] [CrossRef] [Green Version]
  50. Watanabe, M.; Okuda, M.; Tsuji, M.; Inokuma, H. Seroepidemiological Study of Canine Ehrlichial Infections in Yamaguchi Prefecture and Surrounding Areas of Japan. Vet. Parasitol. 2004, 124, 101–107. [Google Scholar] [CrossRef]
  51. Kawahara, M.; Ito, T.; Suto, C.; Shibata, S.; Rikihisa, Y.; Hata, K.; Hirai, K. Comparison of Ehrlichia Muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. Muris as Antigen. J. Clin. Microbiol. 1999, 37, 1123–1129. [Google Scholar] [CrossRef] [Green Version]
  52. Kubo, S.; Tateno, M.; Ichikawa, Y.; Endo, Y. A Molecular Epidemiological Survey of Babesia, Hepatozoon, Ehrlichia and Anaplasma Infections of Dogs in Japan. J. Vet. Med. Sci. 2015, 77, 1275–1279. [Google Scholar] [CrossRef] [Green Version]
  53. Suto, Y.; Suto, A.; Inokuma, H.; Obayashi, H.; Hayashi, T. First Ehrlichia Infection. Vetrecord 2001, 148, 809–812. [Google Scholar]
  54. Inokuma, H.; Beppu, T.; Okuda, M.; Shimada, Y.; Sakata, Y. Epidemiological Survey of Anaplasma Platys and Ehrlichia Canis Using Ticks Collected from Dogs in Japan. Vet. Parasitol. 2003, 115, 343–348. [Google Scholar] [CrossRef] [PubMed]
  55. Suh, G.H.; Ahn, K.S.; Ahn, J.H.; Kim, H.J.; Leutenegger, C.; Shin, S.S. Serological and Molecular Prevalence of Canine Vector-Borne Diseases (CVBDs) in Korea. Parasites Vectors 2017, 10, 1–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Lee, S.O.; Na, D.K.; Kim, C.M.; Li, Y.H.; Cho, Y.H.; Park, J.H.; Lee, J.H.; Eo, S.K.; Klein, T.A.; Chae, J.S. Identification and Prevalence of Ehrlichia Chaffeensis Infection in Haemaphysalis Longicornis Ticks from Korea by PCR, Sequencing and Phylogenetic Analysis Based on 16S RRNA Gene. J. Vet. Sci. 2005, 6, 151–155. [Google Scholar] [CrossRef]
  57. Bell, D.R.; Berghaus, R.D.; Patel, S.; Beavers, S.; Fernandez, I.; Sanchez, S. Seroprevalence of Tick-Borne Infections in Military Working Dogs in the Republic of Korea. Vector Borne Zoonotic Dis. 2012, 12, 1023–1030. [Google Scholar] [CrossRef]
  58. Lim, S.; Irwin, P.J.; Lee, S.; Oh, M.; Ahn, K.; Myung, B.; Shin, S. Comparison of Selected Canine Vector-Borne Diseases between Urban Animal Shelter and Rural Hunting Dogs in Korea. Parasites Vectors 2010, 3, 3–7. [Google Scholar] [CrossRef]
  59. Hwang, C.Y.; Seo, S.H.; Kang, J.G.; Youn, H.Y.; seok Chae, J. Ehrlichia and Borrelia Spp. Infection in German Shepherd Dogs in Korea. J. Vet. Clin. 2011, 28, 204–210. [Google Scholar]
  60. Lee, S.-E.; Song, K.-H.; Lee, S.-H. Survey of Ehrlichia Canis and Borrelia Burgdorferi Antibodies in Dogs (German Shepherd) Reared in Korea. Korean J. Vet. Res. 2007, 47, 281–283. [Google Scholar]
  61. Wu, T.; Sun, H.; Wu, Y.; Huang, H. Prevalence and Risk Factors of Canine Ticks and Tick-Borne Diseases in Taipei, Taiwan. J. Vet. Clin. Sci. 2008, 2, 75–78. [Google Scholar]
  62. Yuasa, Y.; Tsai, Y.L.; Chang, C.C.; Hsu, T.H.; Chou, C.C. The Prevalence of Anaplasma Platys and a Potential Novel Anaplasma Species Exceed That of Ehrlichia Canis in Asymptomatic Dogs and Rhipicephalus Sanguineus in Taiwan. J. Vet. Med. Sci. 2017, 79, 1494–1502. [Google Scholar] [CrossRef] [Green Version]
  63. Yuasa, Y.; Hsu, T.H.; Chou, C.C.; Huang, C.C.; Huang, W.C.; Chang, C.C. The Comparison of Spatial Variation and Risk Factors between Mosquito-Borne and Tick-Borne Diseases: Seroepidemiology of Ehrlichia Canis, Anaplasma Species, and Dirofilaria Immitis in Dogs. Comp. Immunol. Microbiol. Infect. Dis. 2012, 35, 599–606. [Google Scholar] [CrossRef] [PubMed]
  64. Wong, S.S.Y.; Teng, J.L.L.; Poon, R.W.S.; Choi, G.K.Y.; Chan, K.H.; Yeung, M.L.; Hui, J.J.Y.; Yuen, K.Y. Comparative Evaluation of a Point-of-Care Immunochromatographic Test SNAP 4Dx with Molecular Detection Tests for Vector-Borne Canine Pathogens in Hong Kong. Vector-Borne Zoonotic Dis. 2011, 11, 1269–1277. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Little, S.E. Ehrlichiosis and Anaplasmosis in Dogs and Cats. Vet. Clin. N. Am.-Small Anim. Pract. 2010, 40, 1121–1140. [Google Scholar] [CrossRef] [PubMed]
  66. Inokuma, H.; Beppu, T.; Okuda, M.; Shimada, Y.; Sakata, Y. Detection of Ehrlichial DNA in Haemaphysalis Ticks Recovered from Dogs in Japan That Is Closely Related to a Novel Ehrlichia Sp. Found in Cattle Ticks from Tibet, Thailand, and Africa. J. Clin. Microbiol. 2004, 42, 1353–1355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Shibata, S.I.; Kawahara, M.; Rikihisa, Y.; Fujita, H.; Watanabe, Y.; Suto, C.; Ito, T. New Ehrlichia Species Closely Related to Ehrlichia Chaffeensis Isolated from Ixodes Ovatus Ticks in Japan. J. Clin. Microbiol. 2000, 38, 1331–1338. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Galay, R.L.; Manalo, A.A.L.; Dolores, S.L.D.; Aguilar, I.P.M.; Sandalo, K.A.C.; Cruz, K.B.; Divina, B.P.; Andoh, M.; Masatani, T.; Tanaka, T. Molecular Detection of Tick-Borne Pathogens in Canine Population and Rhipicephalus Sanguineus (Sensu Lato) Ticks from Southern Metro Manila and Laguna, Philippines. Parasites Vectors 2018, 11, 643. [Google Scholar] [CrossRef] [Green Version]
  69. Huggins, L.G.; Koehler, A.v.; Ng-Nguyen, D.; Wilcox, S.; Schunack, B.; Inpankaew, T.; Traub, R.J. Assessment of a Metabarcoding Approach for the Characterisation of Vector-Borne Bacteria in Canines from Bangkok, Thailand. Parasites Vectors 2019, 12, 1–11. [Google Scholar] [CrossRef] [Green Version]
  70. Rani, P.A.M.A.; Irwin, P.; Coleman, G.; Gatne, M.; Traub, R. A Survey of Canine Tick-Borne Diseases in India. Para–Sites Vectors 2011, 4, 141. [Google Scholar] [CrossRef] [Green Version]
  71. Nyindo, M.; Huxsoll, D.L.; Ristic, M.; Kakoma, I.; Brown, J.L.; Carson, C.A.; Stephenson, E.H. Cell-Mediated and Humoral Immune Responses of German Shepherd Dogs and Beagles to Experimental Infection with Ehrlichia Canis. Am. J. Vet. Res. 1980, 41, 250–254. [Google Scholar]
  72. Harrus, S.; Kass, P.H.; Klement, E.; Waner, T. Canine Monocytic Ehrlichiosis: A Retrospective Study of 100 Cases, and an Epidemiological Investigation of Prognostic Indicators for the Disease. Vet. Rec. 1997, 141, 360–363. [Google Scholar] [CrossRef]
  73. Costa, L.M.; Rembeck, K.; Ribeiro, M.F.B.; Beelitz, P.; Pfister, K.; Passos, L.M.F. Sero-Prevalence and Risk Indicators for Canine Ehrlichiosis in Three Rural Areas of Brazil. Vet. J. 2007, 174, 673–676. [Google Scholar] [CrossRef] [PubMed]
  74. Rodriguez-Vivas, R.I.; Albornoz, R.E.F.; Bolio, G.M.E. Ehrlichia Canis in Dogs in Yucatan, Mexico: Seroprevalence, Prevalence of Infection and Associated Factors. Vet. Parasitol. 2005, 127, 75–79. [Google Scholar] [CrossRef] [PubMed]
  75. Selim, A.; Alanazi, A.D.; Sazmand, A.; Otranto, D. Seroprevalence and Associated Risk Factors for Vector-Borne Pathogens in Dogs from Egypt. Parasites Vectors 2021, 14, 175. [Google Scholar] [CrossRef] [PubMed]
  76. Angelou, A.; Gelasakis, A.I.; Verde, N.; Pantchev, N.; Schaper, R.; Chandrashekar, R.; Papadopoulos, E. Prevalence and Risk Factors for Selected Canine Vector-Borne Diseases in Greece. Parasites Vectors 2019, 12, 283. [Google Scholar] [CrossRef]
  77. Bowman, D.; Little, S.E.; Lorentzen, L.; Shields, J.; Sullivan, M.P.; Carlin, E.P. Prevalence and Geographic Distribution of Dirofilaria Immitis, Borrelia Burgdorferi, Ehrlichia Canis, and Anaplasma Phagocytophilum in Dogs in the United States: Results of a National Clinic-Based Serologic Survey. Vet. Parasitol. 2009, 160, 138–148. [Google Scholar] [CrossRef]
  78. Moraes-Filho, J.; Krawczak, F.S.; Costa, F.B.; Soares, J.F.; Labruna, M.B. Comparative Evaluation of the Vector Competence of Four South American Populations of the Rhipicephalus Sanguineus Group for the Bacterium Ehrlichia Canis, the Agent of Canine Monocytic Ehrlichiosis. PLoS ONE 2015, 10, e0139386. [Google Scholar] [CrossRef]
  79. Greene, C.E. Infectious Diseases of the Dog and Cat; WB Saunders: Philadelphia, PA, USA; Elsevier Science: Amsterdam, the Netherlands, 2006; ISBN 072160062X. [Google Scholar]
  80. Burgio, F.; Meyer, L.; Armstrong, R. A Comparative Laboratory Trial Evaluating the Immediate Efficacy of Fluralaner, Afoxolaner, Sarolaner and Imidacloprid + Permethrin against Adult Rhipicephalus Sanguineus (Sensu Lato) Ticks Attached to Dogs. Parasit Vectors 2016, 9, 626. [Google Scholar] [CrossRef] [Green Version]
  81. Fourie, J.J.; Stanneck, D.; Luus, H.G.; Beugnet, F.; Wijnveld, M.; Jongejan, F. Transmission of Ehrlichia Canis by Rhipicephalus Sanguineus Ticks Feeding on Dogs and on Artificial Membranes. Vet. Parasitol. 2013, 197, 595–603. [Google Scholar] [CrossRef]
  82. Gray, J.S.; Dautel, H.; Estrada-Peña, A.; Kahl, O.; Lindgren, E. Effects of Climate Change on Ticks and Tick-Borne Diseases in Europe. Interdiscip. Perspect. Infect. Dis. 2009, 2009, 593232. [Google Scholar] [CrossRef]
  83. Gray, J.; Dantas-Torres, F.; Estrada-Peña, A.; Levin, M. Systematics and Ecology of the Brown Dog Tick, Rhipicephalus Sanguineus. Ticks Tick Borne Dis. 2013, 4, 171–180. [Google Scholar] [CrossRef]
  84. Uspensky, I.; Ioffe-Uspensky, I. The Dog Factor in Brown Dog Tick Rhipicephalus Sanguineus (Acari: Ixodidae) Infestations in and near Human Dwellings. Int. J. Med. Microbiol. 2002, 291, 156–163. [Google Scholar] [CrossRef] [PubMed]
  85. Kidd, L.; Breitschwerdt, E.B. Transmission Times and Prevention of Tick-Borne Diseases in Dogs. Compend. Contin. Educ. Pract. Vet.-N. Am. Ed. 2003, 25, 742–753. [Google Scholar]
  86. Bremer, W.G.; Schaefer, J.J.; Wagner, E.R.; Ewing, S.A.; Rikihisa, Y.; Needham, G.R.; Jittapalapong, S.; Moore, D.L.; Stich, R.W. Transstadial and Intrastadial Experimental Transmission of Ehrlichia Canis by Male Rhipicephalus Sanguineus. Vet. Parasitol. 2005, 131, 95–105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  87. Phillips, J. Rocky Mountain Spotted Fever. Workplace Health Saf. 2017, 65, 48. [Google Scholar] [CrossRef] [Green Version]
  88. Ipek, N.D.S.; Özübek, S.; Aktas, M. Molecular Evidence for Transstadial Transmission of Ehrlichia Canis by Rhipicephalus Sanguineus Sensu Lato under Field Conditions. J. Med. Entomol. 2018, 55, 440–444. [Google Scholar] [CrossRef]
  89. Mavromatis, K.; Doyle, C.K.; Lykidis, A.; Ivanova, N.; Francino, M.P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland, A.; et al. The Genome of the Obligately Intracellular Bacterium Ehrlichia Canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies. J. Bacteriol. 2006, 188, 4015–4023. [Google Scholar] [CrossRef] [Green Version]
  90. Paddock, C.D.; Childs, J.E. Ehrlichia Chaffeensis: A Prototypical Emerging Pathogen. Clin. Microbiol. Rev. 2003, 16, 37–64. [Google Scholar] [CrossRef] [Green Version]
  91. Ismail, N.; Bloch, K.C.; McBride, J.W. Human Ehrlichiosis and Anaplasmosis. Clin. Lab. Med. 2010, 30, 261–292. [Google Scholar] [CrossRef] [Green Version]
  92. Tabar, M.D.; Francino, O.; Altet, L.; Sánchez, A.; Ferrer, L.; Roura, X. PCR Survey of Vectorborne Pathogens in Dogs Living in and around Barcelona, an Area Endemic for Leishmaniosis. Vet. Rec. 2009, 164, 112–116. [Google Scholar] [CrossRef]
  93. Egenvall, A.; Bjöersdorff, A.; Lilliehöök, I.; Engvall, E.O.; Karlstam, E.; Artursson, K.; Hedhammar, A.; Gunnarsson, A. Early Manifestations of Granulocytic Ehrlichiosis in Dogs Inoculated Experimentally with a Swedish Ehrlichia Species Isolate. Vet. Rec. 1998, 143, 412–417. [Google Scholar] [CrossRef]
  94. Egenvall, A.E.; Hedhammar, Å.A.; Bjöersdorff, A.I. Clinical Features and Serology of 14 Dogs Affected by Granulocytic Ehrlichiosis in Sweden. Vet. Rec. 1997, 140, 222–226. [Google Scholar] [CrossRef] [PubMed]
  95. McClure, J.C.; Crothers, M.L.; Schaefer, J.J.; Stanley, P.D.; Needham, G.R.; Ewing, S.A.; Stich, R.W. Efficacy of a Doxycycline Treatment Regimen Initiated during Three Different Phases of Experimental Ehrlichiosis. Antimicrob. Agents Chemother. 2010, 54, 5012–5020. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  96. Waner, T.; Harrus, S.; Bark, H.; Bogin, E.; Avidar, Y.; Keysary, A. Characterization of the Subclinical Phase of Canine Ehrlichiosis in Experimentally Infected Beagle Dogs. Vet. Parasitol. 1997, 69, 307–317. [Google Scholar] [CrossRef]
  97. Mylonakis, M.E.; Koutinas, A.F.; Breitschwerdt, E.B.; Hegarty, B.C.; Billinis, C.D.; Leontides, L.S.; Kontos, V.S. Chronic Canine Ehrlichiosis (Ehrlichia Canis): A Retrospective Study of 19 Natural Cases. J. Am. Anim. Hosp. Assoc. 2004, 40, 174–184. [Google Scholar] [CrossRef]
  98. Maggi, R.G.; Birkenheuer, A.J.; Hegarty, B.C.; Bradley, J.M.; Levy, M.G.; Breitschwerdt, E.B. Comparison of Serological and Molecular Panels for Diagnosis of Vector-Borne Diseases in Dogs. Parasites Vectors 2014, 7, 127. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  99. Pérez, C.; Maggi, R.G.; Diniz, P.P.V.P.; Breitschwerdt, E.B. Molecular and Serological Diagnosis of Bartonella Infection in 61 Dogs from the United States. J. Vet. Intern. Med. 2011, 25, 805–810. [Google Scholar] [CrossRef] [PubMed]
  100. Diniz, P.P.V.D.P.; Maggi, R.G.; Schwartz, D.S.; Cadenas, M.B.; Bradley, J.M.; Hegarty, B.; Breutschwerdt, E.B. Canine Bartonellosis: Serological and Molecular Prevalence in Brazil and Evidence of Co-Infection with Bartonella Henselae and Bartonella Vinsonii Subsp. Berkhoffii. Vet. Res. 2007, 38, 697–710. [Google Scholar] [CrossRef] [Green Version]
  101. Cowell, R.L.; Tyler, R.D.; Clinkenbeard, K.D.; Meinkoth, J.H. Ehrlichiosis and Polyarthritis in Three Dogs. J. Am. Vet. Med. Assoc. 1988, 192, 1093–1095. [Google Scholar]
  102. Ecker, D.J.; Massire, C.; Blyn, L.B.; Hofstadler, S.A.; Hannis, J.C.; Eshoo, M.W.; Hall, T.A.; Sampath, R. Molecular Genotyping of Microbes by Multilocus PCR and Mass Spectrometry: A New Tool for Hospital Infection Control and Public Health Surveillance. In Molecular Epidemiology of Microorganisms; Springer: Berlin/Heidelberg, Germany, 2009; pp. 71–87. [Google Scholar]
  103. Codner, E.C.; Farris-Smith, L.L. Characterization of the Subclinical Phase of Ehrlichiosis in Dogs. J. Am. Vet. Med. Assoc. 1986, 189, 47–50. [Google Scholar]
  104. Mylonakis, M.E.; Ceron, J.J.; Leontides, L.; Siarkou, V.I.; Martinez, S.; Tvarijonaviciute, A.; Koutinas, A.F.; Harrus, S. Serum Acute Phase Proteins as Clinical Phase Indicators and Outcome Predictors in Naturally Occurring Canine Monocytic Ehrlichiosis. J. Vet. Intern. Med. 2011, 25, 811–817. [Google Scholar] [CrossRef]
  105. Ybañez, A.P.; Ybañez, R.H.D.; Villavelez, R.R.; Malingin, H.P.F.; Barrameda, D.N.M.; Naquila, S.V.; Olimpos, S.M.B. Retrospective Analyses of Dogs Found Serologically Positive for Ehrlichia Canis in Cebu, Philippines from 2003 to 2014. Vet. World 2016, 9, 43–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  106. Gianopoulos, A.; Mylonakis, M.E.; Theodorou, K.; Christopher, M.M. Quantitative and Qualitative Leukocyte Abnormalities in Dogs with Experimental and Naturally Occurring Acute Canine Monocytic Ehrlichiosis. Vet. Clin. Pathol. 2016, 45, 281–290. [Google Scholar] [CrossRef] [PubMed]
  107. de Castro, M.B.; Machado, R.Z.; de Aquino, L.P.C.T.; Alessi, A.C.; Costa, M.T. Experimental Acute Canine Monocytic Ehrlichiosis: Clinicopathological and Immunopathological Findings. Vet. Parasitol. 2004, 119, 73–86. [Google Scholar] [CrossRef] [PubMed]
  108. Kohn, B.; Galke, D.; Beelitz, P.; Pfister, K. Clinical Features of Canine Granulocytic Anaplasmosis in 18 Naturally Infected Dogs. J. Vet. Intern. Med. 2008, 22, 1289–1295. [Google Scholar] [CrossRef] [PubMed]
  109. Qurollo, B.A.; Davenport, A.C.; Sherbert, B.M.; Grindem, C.B.; Birkenheuer, A.J.; Breitschwerdt, E.B. Infection with Panola Mountain Ehrlichia Sp. in a Dog with Atypical Lymphocytes and Clonal T-Cell Expansion. J. Vet. Intern. Med. 2013, 27, 1251–1255. [Google Scholar] [CrossRef] [PubMed]
  110. Villaescusa, A.; Tesouro, M.A.; García-Sancho, M.; Ayllón, T.; Rodríguez-Franco, F.; Sainz, A. Evaluation of Peripheral Blood Lymphocyte Subsets in Family-Owned Dogs Naturally Infected by Ehrlichia Canis. Comp. Immunol. Microbiol. Infect. Dis. 2012, 35, 391–396. [Google Scholar] [CrossRef]
  111. Rungsipipat, A.; Oda, M.; Kumpoosiri, N.; Wangnaitham, S.; Poosoonthontham, R.; Komkaew, W.; Suksawat, F.; Ryoji, Y. Clinicopathological Study of Experimentally Induced Canine Monocytic Ehrlichiosis. Comp. Clin. Pathol. 2009, 18, 13–22. [Google Scholar] [CrossRef]
  112. Inokuma, H.; Ohno, K.; Onishi, T.; Raoult, D.; Brouqui, P. Detection of Ehrlichial Infection by PCR in Dogs from Yamaguchi and Okinawa Prefectures, Japan. J. Vet. Med. Sci. 2001, 63, 815–817. [Google Scholar] [CrossRef] [Green Version]
  113. Mylonakis, M.E.; Koutinas, A.F.; Billinis, C.; Leontides, L.S.; Kontos, V.; Papadopoulos, O.; Rallis, T.; Fytianou, A. Evaluation of Cytology in the Diagnosis of Acute Canine Monocytic Ehrlichiosis (Ehrlichia Canis): A Comparison between Five Methods. Vet. Microbiol. 2003, 91, 197–204. [Google Scholar] [CrossRef]
  114. Mylonakis, M.E.; Borjesson, D.L.; Leontides, L.; Siarkou, V.I.; Theodorou, K.; Koutinas, A.F. Cytologic Patterns of Lymphadenopathy in Canine Monocytic Ehrlichiosis. Vet. Clin. Pathol. 2011, 40, 78–83. [Google Scholar] [CrossRef]
  115. Nicholson, W.L.; Allen, K.E.; McQuiston, J.H.; Breitschwerdt, E.B.; Little, S.E. The Increasing Recognition of Rickettsial Pathogens in Dogs and People. Trends Parasitol. 2010, 26, 205–212. [Google Scholar] [CrossRef] [PubMed]
  116. Nair, A.D.S.; Cheng, C.; Ganta, C.K.; Sanderson, M.W.; Alleman, A.R.; Munderloh, U.G.; Ganta, R.R. Comparative Experimental Infection Study in Dogs with Ehrlichia Canis, E. Chaffeensis, Anaplasma Platys and A. Phagocytophilum. PLoS ONE 2016, 11, e0148239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  117. Harvey, J.W.; Simpson, C.F.; Gaskin, J.M. Cyclic Thrombocytopenia Induced by a Rickettsia-like Agent in Dogs. J. Infect. Dis. 1978, 137, 182–188. [Google Scholar] [CrossRef] [PubMed]
  118. Waner, T.; Harrus, S.; Jongejan, F.; Bark, H.; Keysary, A.; Cornelissen, A.W.C.A. Significance of Serological Testing for Ehrlichial Diseases in Dogs with Special Emphasis on the Diagnosis of Canine Monocytic Ehrlichiosis Caused by Ehrlichia Canis. Vet Parasitol 2001, 95, 1–15. [Google Scholar] [CrossRef] [PubMed]
  119. Harrus, S.; Alleman, A.R.; Bark, H.; Mahan, S.M.; Waner, T. Comparison of Three Enzyme-Linked Immunosorbant Assays with the Indirect Immunofluorescent Antibody Test for the Diagnosis of Canine Infection with Ehrlichia Canis. Vet. Microbiol. 2002, 86, 361–368. [Google Scholar] [CrossRef]
  120. da Costa, P.S.G.; Brigatte, M.E.; Greco, D.B. Antibodies to Rickettsia Rickettsii, Rickettsia Typhi, Coxiella Burnetii, Bartonella Henselae, Rartonella Quintana and Eirlichia Chaffeensis among Healthy Population in Minas Gerais, Brazil. Mem. Inst. Oswaldo Cruz 2005, 100, 853–859. [Google Scholar] [CrossRef] [PubMed]
  121. Gaunt, S.D.; Beall, M.J.; Stillman, B.A.; Lorentzen, L.; Diniz, P.P.V.P.; Chandrashekar, R.; Breitschwerdt, E.B. Experimental Infection and Co-Infection of Dogs with Anaplasma Platys and Ehrlichia Canis: Hematologic, Serologic and Molecular Findings. Parasites Vectors 2010, 3, 33. [Google Scholar] [CrossRef] [Green Version]
  122. Harrus, S.; Waner, T.; Aizenberg, I.; Bark, H. Therapeutic Effect of Doxycycline in Experimental Subclinical Canine Monocytic Ehrlichiosis: Evaluation of a 6-Week Course. J. Clin. Microbiol. 1998, 36, 2140–2142. [Google Scholar] [CrossRef] [Green Version]
  123. Solano-Gallego, L.; Llull, J.; Osso, M.; Hegarty, B.; Breitschwerdt, E. A Serological Study of Exposure to Arthropod-Borne Pathogens in Dogs from Northeastern Spain. Vet. Res. 2006, 37, 231–244. [Google Scholar] [CrossRef] [Green Version]
  124. Johnson, E.M.; Ewing, S.A.; Barker, R.W.; Fox, J.C.; Crow, D.W.; Kocan, K.M. Experimental Transmission of Ehrlichia Canis (Rickettsiales: Ehrlichieae) by Dermacentor Variabilis (Acari: Ixodidae). Vet. Parasitol. 1998, 74, 277–288. [Google Scholar] [CrossRef]
  125. Perez, M.; Rikihisa, Y.; Wen, B. Ehrlichia Canis-like Agent Isolated from a Man in Venezuela: Antigenic and Genetic Characterization. J. Clin. Microbiol. 1996, 34, 2133–2139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  126. Doyle, C.K.; Labruna, M.B.; Breitschwerdt, E.B.; Tang, Y.W.; Corstvet, R.E.; Hegarty, B.C.; Bloch, K.C.; Li, P.; Walker, D.H.; McBride, J.W. Detection of Medically Important Ehrlichia by Quantitative Multicolor TaqMan Real-Time Polymerase Chain Reaction of the Dsb Gene. J. Mol. Diagn. 2005, 7, 504–510. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  127. Gardner, I.A.; Colling, A.; Caraguel, C.; Crowther, J.R.; Jones, G.; Firestone, S.M.; Heuer, C. Introduction—Validation of Tests for OIE-Listed Diseases as Fit-for-Purpose in a World of Evolving Diagnostic Technologies. Rev. Sci. Et Tech. De L’oie 2021, 40, 19–28. [Google Scholar] [CrossRef] [PubMed]
  128. Harrus, S.; Kenny, M.; Miara, L.; Aizenberg, I.; Waner, T.; Shaw, S. Comparison of Simultaneous Splenic Sample PCR with Blood Sample PCR for Diagnosis and Treatment of Experimental Ehrlichia Canis Infection. Antimicrob. Agents Chemother. 2004, 48, 4488–4490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  129. Breitschwerdt, E.B.; Hegarty, B.C.; Hancock, S.I. Doxycycline Hyclate Treatment of Experimental Canine Ehrlichiosis Followed by Challenge Inoculation with Two Ehrlichia Canis Strains. Antimicrob. Agents Chemother. 1998, 42, 362–368. [Google Scholar] [CrossRef] [Green Version]
  130. Wen, B.; Rikihisa, Y.; Mott, J.M.; Greene, R.; Kim, H.Y.; Zhi, N.; Couto, G.C.; Unver, A.; Bartsch, R. Comparison of Nested PCR with Immunofluorescent-Antibody Assay for Detection of Ehrlichia Canis Infection in Dogs Treated with Doxycycline. J. Clin. Microbiol. 1997, 35, 1852–1855. [Google Scholar] [CrossRef] [Green Version]
  131. Neer, T.M.; Breitschwerdt, E.B.; Greene, R.T.; Lappin, M.R. Consensus Statement on Ehrlichial Disease of Small Animals from the Infectious Disease Study Group of the ACVIM. J. Vet. Intern. Med. 2002, 16, 309–315. [Google Scholar] [CrossRef]
  132. Jenkins, S.; Ketzis, J.K.; Dundas, J.; Scorpio, D. Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia Canis Infection in Dogs. J. Vet. Intern. Med. 2018, 32, 217–221. [Google Scholar] [CrossRef] [Green Version]
  133. Mylonakis, M.E.; Harrus, S.; Breitschwerdt, E.B. An Update on the Treatment of Canine Monocytic Ehrlichiosis (Ehrlichia Canis). Vet. J. 2019, 246, 45–53. [Google Scholar] [CrossRef]
  134. Eddlestone, S.M.; Neer, T.M.; Gaunt, S.D.; Corstvet, R.; Gill, A.; Hosgood, G.; Hegarty, B.; Breitschwerdt, E.B. Failure of Imidocarb Dipropionate to Clear Experimentally Induced Ehrlichia Canis Infection in Dogs. J. Vet. Intern. Med. 2006, 20, 840–844. [Google Scholar] [CrossRef]
  135. Kelly, P.J.; Matthewman, L.A.; Brouqui, P.; Raoult, D. Lack of Susceptibility of Ehrlichia Canis to Imidocarb Dipropionate in Vitro. J. S. Afr. Vet. Assoc. 1998, 69, 55–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  136. Schaefer, J.J.; Kahn, J.; Needham, G.R.; Rikihisa, Y.; Ewing, S.A.; Stich, R.W. Antibiotic Clearance of Ehrlichia Canis from Dogs Infected by Intravenous Inoculation of Carrier Blood. Ann. N. Y. Acad. Sci. 2008, 1149, 263–269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  137. Theodorou, K.; Mylonakis, M.E.; Siarkou, V.I.; Leontides, L.; Koutinas, A.F.; Koutinas, C.K.; Kritsepi-Konstantinou, M.; Batzias, G.; Flouraki, E.; Eyal, O.; et al. Efficacy of Rifampicin in the Treatment of Experimental Acute Canine Monocytic Ehrlichiosis. J. Antimicrob. Chemother. 2013, 68, 1619–1626. [Google Scholar] [CrossRef] [PubMed]
  138. Fourie, J.J.; Horak, I.; Crafford, D.; Erasmus, H.L.; Botha, O.J. The Efficacy of a Generic Doxycycline Tablet in the Treatment of Canine Monocytic Ehrlichiosis. J. S. Afr. Vet. Assoc. 2015, 86, 10. [Google Scholar] [CrossRef] [Green Version]
  139. Neer, T.M.; Eddlestone, S.M.; Gaunt, S.D.; Corstvet, R.E. Efficacy of Enrofloxacin for the Treatment of Experimentally Induced Ehrlichia Canis Infection. J. Vet. Intern. Med. / Am. Coll. Vet. Intern. Med. 1999, 13, 501–504. [Google Scholar] [CrossRef]
  140. Bartsch, R.C.; Greene, R.T. Post-Therapy Antibody Titers in Dogs with Ehrlichiosis: Follow-up Study on 68 Patients Treated Primarily with Tetracycline and/or Doxycycline. J. Vet. Intern. Med. 1996, 10, 271–274. [Google Scholar] [CrossRef]
  141. de Tommasi, A.S.; Otranto, D.; Dantas-Torres, F.; Capelli, G.; Breitschwerdt, E.B.; de Caprariis, D. Are Vector-Borne Pathogen Co-Infections Complicating the Clinical Presentation in Dogs? Parasites Vectors 2013, 6, 95–97. [Google Scholar] [CrossRef] [Green Version]
  142. Dantas-Torres, F.; Otranto, D. Dogs, Cats, Parasites, and Humans in Brazil: Opening the Black Box. Parasites Vectors 2014, 7, 22. [Google Scholar] [CrossRef] [Green Version]
  143. Jongejan, F.; de Vos, C.; Fourie, J.J.; Beugnet, F. A Novel Combination of Fipronil and Permethrin (Frontline Tri-Act®/Frontect®) Reduces Risk of Transmission of Babesia Canis by Dermacentor Reticulatus and of Ehrlichia Canis by Rhipicephalus Sanguineus Ticks to Dogs. Parasites Vectors 2015, 8, 602. [Google Scholar] [CrossRef] [Green Version]
  144. Jongejan, F.; Crafford, D.; Erasmus, H.; Fourie, J.J.; Schunack, B. Comparative Efficacy of Oral Administrated Afoxolaner (NexGardTM) and Fluralaner (BravectoTM) with Topically Applied Permethrin/Imidacloprid (Advantix®) against Transmission of Ehrlichia Canis by Infected Rhipicephalus Sanguineus Ticks to Dogs. Parasites Vectors 2016, 9, 348. [Google Scholar] [CrossRef] [Green Version]
  145. Davoust, B.; Keundjian, A.; Rous, V.; Maurizi, L.; Parzy, D. Validation of Chemoprevention of Canine Monocytic Ehrlichiosis with Doxycycline. Vet. Microbiol. 2005, 107, 279–283. [Google Scholar] [CrossRef] [PubMed]
Vetsci 10 00021 g001 550
Figure 1. Prevalence percentage and main vector responsible for ehrlichiosis in dogs reported in different countries of east and south Asia.
Figure 1. Prevalence percentage and main vector responsible for ehrlichiosis in dogs reported in different countries of east and south Asia.
Vetsci 10 00021 g001
Table
Table 1. Prevalence studies on ehrlichiosis in dogs conducted in south and east Asian countries.
Table 1. Prevalence studies on ehrlichiosis in dogs conducted in south and east Asian countries.
Country/RegionSample SourceCausative Agent/SpeciesDiagnostic MethodPrevalence %
(Positive/Total Number of Samples)		Reference
South Asia
Pakistan
Blood
Ehrlichia canis
PCR
28 (42/151)		[26]
PakistanBloodEhrlichia canisPCR24.5 (12/49)[27]
IndiaBloodEhrlichia canisPCR8 (12/150)[28]
IndiaBloodEhrlichia canisPCR8.40 (70/833)[29]
IndiaTicks
Blood		Ehrlichia canis
Ehrlichia canis		PCR
PCR		16.1
16.9		[30]
IndiaBloodEhrlichia canisPCR30 (18/60)[22]
IndiaBloodEhrlichia canisPCR41.59 (89/214)[31]
IndiaBlood
Serum		Ehrlichia sp.
Ehrlichia canis		Microscopy
ELISA		14.28 (12/84)
86.90 (73/84)		[24]
IndiaBlood
Blood		Ehrlichia sp.
Ehrlichia canis		Microscopy
PCR		19.38 (19/98)
50 (49/98)		[32]
IndiaBloodEhrlichia canisPCR0.39 (3/778)[33]
IndiaSerumEhrlichia canisELISA48.33 (29/60)[34]
IndiaBloodEhrlichia canisPCR20.6[14]
IndiaSerum
Blood		Ehrlichia canis
Ehrlichia canis		ELISA
PCR		57.5 (293/510)
8.8 (45/510)		[35]
IndiaBlood
Serum
Blood		Ehrlichia canis
Ehrlichia canis
Ehrlichia canis		Microscopy
ELISA
PCR		1.33 (3/225)
19.11 (43/225)
5.78 (13/225)		[36]
IndiaSerumEhrlichia canisELISA19 (9/48)[37]
NepalBloodEhrlichia canisPCR27.14 (19/70)[38]
NepalBloodEhrlichia spp.Microscopy8 (4/50)[39]
BangladeshBloodAnaplasma/
Ehrlichia spp.		PCR2.9 (3/68)[40]
East Asia
People’s Republic of China (PRC)		SerumEhrlichia canisELISA1.29 (4/309)[41]
PRCBlood
Blood		Ehrlichia canis
Ehrlichia canis		PCR
PCR		12.12 (36/297)
15.23 (108/709)		[42]
PRCBlood
Ticks		Ehrlichia canis
Ehrlichia canis		PCR
PCR		1.4 (15/1114)
4.1 (6/146)		[43]
PRCTicks
Serum		Ehrlichia canis
Ehrlichia canis
Ehrlichia canis
Ehrlichia canis		PCR
PCR
PCR
ELISA		11.03 (50/453)
3.29 (3/91)
13.69 (10/73)
1.33 (7/526)		[44]
PRCSerumEhrlichia canisSNAP test (EISA)2.17 (13/600)[45]
PRCTicksEhrlichia canisPCR0.97 (3/308)[46]
PRCTicksEhrlichia spp. (E.canis and E.muris like)PCR28.7 (24/849)[47]
PRCBloodEhrlichia canisELISA1.9%[48]
PRCBloodEhrlichia canisPCR0.0 (0/162)[49]
JapanSerumEhrlichia canis
Ehrlichia chaffeensis
Ehrlichia muris		IFA
IFA
IFA		18 (27/150)
18.7 (28/150)
11.3 (17/150)		[50]
JapanTicksEhrlichia platysPCR9.4 (3/32)[51]
JapanBloodEhrlichia platysPCR1.5 (1/67) Yamaguchi
27.6 (24/87)
Okinawa		[51]
JapanSerumEhrlichia murisIFA3.6 (18/499)[52]
JapanBloodEhrlichia spp./Anaplasma
spp.		PCR1.5 (11/722)[53]
JapanBloodEhrlichia canisPCR+
Electron Microscopy		100 (1/1)[54]
JapanTicksEhrlichia sppPCR0.25 (3/1211)[55]
JapanTicksEhrlichia canisPCR0.0 (0/1211)[55]
South KoreaSerum
Blood		Ehrlichia canis
Ehrlichia canis		SNAP test (ELISA)
PCR		4.7 (25/532)
0.0 (0/25)		[56]
South KoreaSerumEhrlichia spp. (E. canis/E. ewingii)
Ehrlichia chaffeensis		ELISA/IFA
ELISA/IFA		10.3 (228/2215)
2.3 (52/2215)		[57]
South KoreaSerum
Serum
Blood		Ehrlichia canis
Ehrlichia canis
Ehrlichia canis		ELISA
IFA
PCR		0.6 (1/182)
22.5 (41/182)
0.0 (0/182)		[58]
South KoreaBloodEhrlichia canisELISA6.1 (14/229) Rural dogs
0.0 (0/692) Urban dogs		[59]
South KoreaSerum
Blood		Ehrlichia spp
Ehrlichia chaffeensis		ELISA
PCR		7.56 (22/291)
3.09 (9/291)		[60]
South KoreaBloodEhrlichia chaffeensisPCR100 (2/2)[5]
South KoreaTicksEhrlichia chaffeensisPCR4.2% (26/611)[57]
South KoreaBloodEhrlichia canis(ELISA)12.3 (29/236)[61]
South KoreaTicks Ehrlichia canis
Ehrlichia chaffeensis		PCR
PCR		0.0 (0/1110)
0.0 (0/1110)		[25]
ROC TaiwanBloodEhrlichia canisELISA2 (2/101)[62]
ROC TaiwanBloodEhrlichia canisELISA1.5[48]
ROC TaiwanBloodEhrlichia canisELISA9.9 (34/344)[63]
ROC TaiwanBlood
Blood
Ticks 		Ehrlichia canis Ehrlichia canis Ehrlichia canisELISA
PCR
PCR		11.4 (20/175)
8.6 (15/175)
1 (3/306)		[64]
Hong Kong SAR, ChinaBloodEhrlichia canisPCR8 (8/100) stray
6 (6/100) Pet		[65]
Table
Table 2. Reported tick species carrying ehrlichiosis in south and east Asian countries/regions.
Table 2. Reported tick species carrying ehrlichiosis in south and east Asian countries/regions.
Country/Region.Tick VectorReference
IndiaRhipicephalus sanguineus,
Rhipicephalus haemaphysaloides		[30]
People’s Republic of China (PRC)Rhipicephalus sanguineus
Haemaphysalis longicornis,
Rhipicephalus haemaphysaloides
Haemaphysalis bispinosa		[43,44,46,47]
JapanRhipicephalus sanguineus
Haemaphysalis flava		[79,80]
South KoreaHaemaphysalis longicornis
Ixodes nipponensis		[25,57]
ROC TaiwanHaemaphysalis hystricis Haemaphysalis longicornis[64]
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Aziz, M.U.; Hussain, S.; Song, B.; Ghauri, H.N.; Zeb, J.; Sparagano, O.A. Ehrlichiosis in Dogs: A Comprehensive Review about the Pathogen and Its Vectors with Emphasis on South and East Asian Countries. Vet. Sci. 2023, 10, 21. https://doi.org/10.3390/vetsci10010021

AMA Style

Aziz MU, Hussain S, Song B, Ghauri HN, Zeb J, Sparagano OA. Ehrlichiosis in Dogs: A Comprehensive Review about the Pathogen and Its Vectors with Emphasis on South and East Asian Countries. Veterinary Sciences. 2023; 10(1):21. https://doi.org/10.3390/vetsci10010021

Chicago/Turabian Style

Aziz, Muhammad Umair, Sabir Hussain, Baolin Song, Hammad Nayyar Ghauri, Jehan Zeb, and Olivier Andre Sparagano. 2023. "Ehrlichiosis in Dogs: A Comprehensive Review about the Pathogen and Its Vectors with Emphasis on South and East Asian Countries" Veterinary Sciences 10, no. 1: 21. https://doi.org/10.3390/vetsci10010021

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