Clinical case presentation and a review of the literature of canine onchocercosis by Onchocerca lupi in the United States
© Otranto et al.; licensee BioMed Central. 2015
Received: 10 December 2014
Accepted: 26 January 2015
Published: 8 February 2015
Onchocerca lupi, a filarioid of zoonotic concern, infects dogs and cats causing ocular lesions of different degrees, from minor to severe. However, infected animals do not always display overt clinical signs, rendering the diagnosis of the infection obscure to the majority of veterinarians. Canine onchocercosis has been reported in the Old World and the information on its occurrence in the United States, as well as its pathogenesis and clinical management is still meagre. This study reports on the largest case series of O. lupi infection from the United States and reviews previous cases of canine onchocercosis in this country.
Information on the clinical history of a series of eight cases of O. lupi infection in dogs diagnosed in Minnesota, New Mexico, Colorado and Florida, from 2011 to 2014, was obtained from clinical records provided the veterinary practitioners. Nematodes were morphologically identified at species level and genetically analyzed.
All dogs displayed a similar clinical presentation, including subconjunctival and episcleral nodules, which were surgically removed. Each dog was subjected to post-operative therapy. Whitish filaria-like parasites were morphologically and molecularly identified as O. lupi.
This study confirms that O. lupi is endemic in the United States, indicating that the distribution of the infection is probably wider than previously thought. With effect, further studies are urgently needed in order to improve the diagnosis and to assess the efficacy of therapeutic protocols, targeting the parasite itself and/or its endosymbionts.
Some filarioids (Spirurida, Onchocercidae) represent a major threat for human health, causing debilitating and socially stigmatizing life-threatening conditions, mainly in developing countries . This is the case of Wuchereria bancrofti and Onchocerca volvulus, the agents of human lymphatic filariasis and river blindness, respectively, which are included in the WHO's priority list of the neglected tropical diseases [2,3]. Meanwhile, human infections by zoonotic filarioids are being more and more often reported worldwide , due to a plethora of environmental and anthropic factors allowing the spreading of arthropod vectors [5,6]. This has been recognized for the canine Dirofilaria immitis and Dirofilaria repens, whose mosquito vectors are prevalent in the same environments [5,7,8]. The role of dogs as reservoir hosts for zoonotic nematodes has spurred the interest of the scientific community towards the study of other species, which may parasitize domestic animals . For example, Onchocerca lupi infects the ocular tissues of dogs and cats [9,10] causing from minor to severe ocular lesions [9,11]. In the initial stage, canine onchocercosis is associated with nonspecific ocular discomfort (i.e., excessive lacrimation, photophobia, conjunctivitis, exophthalmos and periorbital swelling) [9,12,13], while, in the chronic phase the typical nodules are detected on the external parts of the ocular apparatus (i.e., eyelids, nictitans, conjunctiva, and sclera) [9,14,15]. However, dogs do not always display overt clinical signs if O. lupi adults develop in the retrobulbar space of the eye [11,13]. Accordingly, the diagnosis of O. lupi relies on the detection of microfilariae in skin snips  and may also be investigated by the use of imaging tools (i.e., ultrasound scans, computed tomography) .
In the United States, cases of canine onchocercosis have been reported since the 90s in California, Utah and Arizona [17-19] but nematodes were not identified at species level. The tentative identification of the parasites in the cases above as Onchocerca lienalis has been questioned  based on the following circumstantial evidence: i) the site of the infection (i.e., filarioids were detected in the ocular region while O. lienalis localizes to the gastro-splenic ligament area of cattle); ii) the failure of experimental infection of dogs with this filarioid species . In addition, the occurrence of gravid female nematodes in the patients above suggested that dogs were most likely the primary/proper host for those parasites, as is the case for O. lupi. The morphological and molecular identification of O. lupi in dogs and cats from the southwestern states (i.e., Colorado, California, Utah, Nevada) [10,20,21] raised the hypothesis that this parasite was implicated also in the cases above. Finally, the first zoonotic case of O. lupi in Arizona  has renewed the interest about this parasite, which has also been increasingly found in humans in the Old World [22-25].
The information on the pathogenesis of canine onchocercosis is still minimal and little data is available on the clinical management of O. lupi. Therefore, this article documents the clinical presentation and the treatment of a series of recently reported cases of canine onchocercosis from the Unites States (i.e., Minnesota, New Mexico, Colorado and Florida) , along with a review of canine onchocercosis in this country.
Clinical history and case outcome
Information on the clinical history of a series of eight cases of O. lupi infection in dogs diagnosed in the Minnesota, New Mexico, Colorado and Florida, from 2011 to 2014, was obtained from clinical records provided by the veterinary practitioners in charge for each case. Information on treatment and case outcome was also provided. All medical procedures were performed after obtaining the owner consent.
Cases on canine onchocercosis diagnosed in the United States, published in the literature were also reviewed. In particular, data on the sex, age, geographical origin, travel history, localization of the nodules and parasite identification for each individual case was analyzed from articles published in the international literature, from 1991 to 2014 [12,17-20,26].
Morphological and molecular identification
Nematodes collected were morphologically identified at species level based on  and . In addition, specimens extracted from dogs 2 and 3 were molecularly processed. Following the genomic DNA extraction by DNeasy Blood & Tissue Kit (Qiagen, GmbH, Hilden, Germany), partial cytochrome oxidase subunit 1 (cox1) and 12S rDNA genes were amplified and sequenced as described elsewhere .
Clinical history and case outcome
An 8-year-old female dog, rescued in Hollywood (Florida) on June 2014, was presented to a local ophthalmologist due to the onset of conjunctival granulomas, which were surgically removed and histologically examined. The animal was treated for heartworm with ivermectin (400 μg/kg orally every day, for 30 days) and fenbendazole (100 mg/kg orally once daily). A few months later, conjunctival lesions reoccurred OU and the animal underwent a second surgery during which nematodes were extracted. Samples were sent to Cornell University to be morphologically and molecularly identified. A gravid female worm was morphologically identified as Onchocerca sp. and microfilariae sent to the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA).
A 2-year-old female mix breed was examined on June 2014. The dog was originally from Farmington (New Mexico), where she was adopted about six weeks before. The animal was apparently healthy, apart for a slight squinting and disconformity in the size of the eyes. The animal was heartworm antigen negative. At the ophthalmic examination, the eyes presented numerous inflammatory conjunctival follicles, mild epiphora, mild diffuse conjunctival hyperemia and soft episcleral swellings in the temporal quadrant, larger in the right eye. During the incisional biopsy, some nematodes were detected and extracted. Oral treatment with ivermectin (400 μg/kg orally once a month for six months) and doxycycline (100 mg/kg orally once daily for three months) was performed. The animal was followed-up three months later and did not show any relapse.
A 3-year-old neutered male Yorkshire terrier dog from Farmington (New Mexico) was presented on May 2014 due to moderate chemosis and to an episcleral flocculent mass in the lateral portion in the right eye. The animal was heartworm antigen negative. A subconjunctival exploratory was performed and multiple thread-like nematodes were removed from the episcleral region in the right eye. The animal underwent the same therapeutic protocol and recheck examinations of case 4, being completely healthy at each follow-up.
A 5-year-old neutered male German shepherd dog from Farmington (New Mexico) was presented on April 2011 due to chronic conjunctivitis in the left eye. Ophthalmic findings revealed a large flocculent episcleral mass in the left eye, occupying the entirety of the ventral episcleral mass and extending distally past the equatorial portion of the globe. The animal was diagnosed with keratoconjunctivitis sicca (KCS) but was heartworm antigen negative. A subconjunctival exploratory surgery was then performed and several thread-like nematodes were removed from the left eye. The animal was treated as in the cases above, along with tacrolimus (0.03% in both eyes, twice daily) to address the KCS and was monthly rechecked for a period of four months. One year following the last monthly recheck examination, the dog displayed recurrence of conjunctivitis in the left eye, exhibiting moderate chemosis of the ventral bulbar conjunctiva. A second subconjunctival exploratory surgery was performed but no nematodes were detected. Monthly recheck examinations were performed for a period of three months. At each of these rechecks moxydectin was administered (0.22 mg/kg subcutaneously). Additional postoperative therapy was doxycycline, doxycycline (5 mg/kg orally twice daily for three months) and neopolydex in both eyes, three times daily. Following monthly recheck examinations and the final moxydectin injection, prophylactic oral anthihelmintic therapy with ivermectin was initiated at 400 μg/kg orally every day for 30 days and recommended for life. The dog remained disease free.
Morphological and molecular identification
Specimens presented external round transverse ridges and two transverse striae per each outer ridge interval, with a typical body diameter/ridge distance interval of 7–10:1 . The nematode morphology and the sequencing of barcoding genes of parasites obtained from cases 2 and 3 were concordant in identifying the specimens recovered from all cases herein reported as O. lupi. In addition, a 100% nucleotide sequence homology was recorded between pcox1  and 12S rDNA sequences herein obtained (AN: KP283474 and KP283475) and those of specimens collected from dogs and cats from different states within the United States (cox1: JX080028- JX080031, JF758473-JF758475, KC763785-KC763786; 12S rDNA: KC763783).
Canine onchocercosis in the USA: review of cases described in the literature and present report, along with data on the geographical origin, location of lesions and diagnosis
Sex (Age in years)
Geographic origin (Travel)
Localization of the nodule (eye)
Reference in the text
Sclera (OD, then OS)
Los Angeles, California
Conjunctiva, Sclera (OS, then OD)
Free worm in the cornea
Retrobulbar space (OD)
California (Washington, Idaho, Nevada)
Las Vegas, Nevada
Oronoco, Minnesota (Durango, Colorado)
Englewood, Colorado (New Mexico)
Englewood, Colorado (Farmington, New Mexico)
Farmington, New Mexico
Farmington, New Mexico
Jemez, New Mexico
Sclera (OS, then OD)
Farmington, New Mexico
Sclera (OS, relapsing)
Consequently, the epidemiology of O. lupi in the United States deserves to be thoroughly assessed since it is likely more widely distributed than currently believed. Indeed, all the reports above were characterized by nodular lesions, but, in the only large epidemiological study performed in Portugal and Greece, where clinical cases were reported, up to 8.4% of the examined animals scored positive for O. lupi microfilariae . Certainly, a serological tool for the diagnosis of O. lupi  would overcome the difficulties related with the detection of microfilariae in the skin snip biopsy, which is an invasive procedure and of limited usefulness during the prepatent period of the infection. Today, the skin-snip for the detection of skin-dwelling microfilariae is the most sensitive procedure for the diagnosis in asymptomatic dogs. This tool should be used for screening dogs relocated from endemic areas, such as New Mexico, to other regions.
Cases herein reported were characterized by a similar clinical presentation, which included subconjunctival and episcleral nodules. In addition, all dogs examined were adults (from three to nine years of age), which may be due to the fact that the incubation period of O. lupi infection is usually long , as already described for O. volvulus (i.e., up to 18 months) . The negative results obtained with the heartworm antigen tests suggest that commercial kits used for screening D. immitis infection are not able to detect cross-reactions with O. lupi. Accordingly, since some of the dogs herein examined underwent chemoprophylactic treatment for the canine heartworm disease with ivermectin, this therapy is most likely ineffective against O. lupi. Indeed, to date the only treatment with reputed efficacy for ocular onchocercosis is represented by the surgical removal of the parasitic nodule followed by post-operative therapeutic administration of melarsomine (2.5 mg/kg intramuscularly, daily for two days), ivermectin (50 μg/kg subcutaneously, one month after the initial treatment), topical antibiotics and systemic prednisolone [12,14]. The above pharmaceutical treatment has been successfully applied to control the relapse of nodules up to more than one year of follow-up. However, although Wolbachia endosymbionts were detected in O. lupi [10,15,29] any chemoprophylactic combination of tetracyclines with macrocyclic lactones has never been tested. Indeed, the use of doxycycline targeting the Wolbachia endosymbionts of filariae was effective in damaging and even killing D. immitis adult worms  and succeeded in eliminating adults of D. immitis, eventually reducing the risk of thromboembolism [31,32]. Similarly, a combination of doxycycline hyclate (10 mg/kg twice daily for 30 days) and ivermectin (6 μg/kg every 15 days for six months) was effective for treating microfilariaemia in dogs affected by D. repens, a cause of subcutaneous dirofilariosis .
Data herein reported indicate that O. lupi may be a risk for human health. Along with the human case reported from Arizona , other cases of human onchocercosis have been diagnosed in Arizona, Colorado, Minnesota and Pennsylvania [21,34]. Therefore, further studies are urgently needed in order to improve the diagnosis of O. lupi infection infection, to better define its pathogenesis, and to report the efficacies of therapeutic protocols, based on controlled clinical trials. These studies should target the parasite itself and/or its endosymbionts.
The authors wish to thank Merial, France for supporting the publication costs of this article.
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