Onchocerca lupi

Synopsis

CAPC Recommends

• Onchocerca lupi is a zoonotic filarial nematode found in ocular and adnexal tissues of dogs and cats.
• Dogs, cats and humans originating from or with travel history to the southwestern United States, Mariana Islands, Europe and the Mediterranean region should be considered at a heightened risk and suspicion for possible infection with Onchocerca lupi.
• Although the majority of infected dogs are often asymptomatic, the diagnosis of O. lupi is most often achieved by a detailed ophthalmic evaluation and detection of ocular nodules, subconjuctival threadlike parasites or threadlike fragments, histopathological identification of adult worms, and by identification of microfilariae from skin snip biopsies.
• Skin microfilariae if present may need to be differentiated from other skin microfilariae such as Cercopithifilaria spp. and potentially Acanthocheilonema reconditum or Dirofilaria immitis.
• For prevention, monthly prophylaxis for heartworm is recommended for all dogs but effectiveness against Onchocerca lupi infection is unknown.

Species

Canine

Onchocerca lupi

Overview of life cycle and stages

• Adults of Onchocerca lupi are found embedded in ocular nodules and granulomatous masses of infected dogs.
• Gravid females release microfilariae (100-117.6 μm) found in the skin primarily of the ears, nose, intrascapular, periocular and umbilical regions of the dog. Microfilariae are found in the greatest numbers during the afternoon and decreasing into the night and morning.
• The microfilariae are ingested during blood feeding by the arthropod vector where they develop to the infective third stage larvae (L3) and are transmitted to a canine or feline host during the next blood meal.
• Currently the arthropod vector is unknown but is suspected to be a black fly (Simulium spp.) or biting midge (Culicoides spp.) species.
• The ingested microfilariae development to the infective stage in the insect vector is likely dependent on the ambient temperature. Transmission of the infective stage to a canine host occurs during the next feeding period.
• Route of somatic migration within the canine host, time of infection to arrival in the ocular tissues, and time before microfilariae are patent in the skin are currently unknown.

Disease

• Epidemiological surveys in Europe found that infected dogs are often asymptomatic, with no clinical changes of the eyes if adult worms are localized to the retrobulbar space and likely not detectable by ophthalmic examination.
• When present, canine ocular onchocerciasis presents with either acute or chronic ocular clinical signs. Those clinical signs described in dogs, are listed below (Grácioet al. 2015).
• Ocular disease in acute canine infections have exhibited the following clinical signs: red eye, conjunctivitis, mild to severe periorbital swelling, exophthalmia, blepharitis, photophobia, lacrimation, serous or mucopurulent discharge, protrusion of the nictitating membrane, diffuse corneal stromal oedema, corneal ulcers and anterior and/or posterior uveitis and in many cases worms were visible on the surface or under the conjunctiva, ocular and periocular tissues.
• Ocular disease in chronic canine infections had worms generally found in pea to cherry-sized subconjunctival granulomatous nodules or cyst-like formations penetrating the retrobulbar space, orbital fascia, eyelid, conjunctiva nictitating membrane and sclera with exophthalmia, and additional presentation with lacrimation, photophobia ocular discharge, corneal oedema, anterior uveitis and secondary glaucoma.

Host association and transmission between hosts

• The insect vector becomes infected after feeding on an infected microfilaremic host (dog) and after development to the infective stage is transmitted to a new host by the vector during the subsequent meal.
• The blackfly Simulium tribulatum has been implicated as an insect vector in southern California, although other blackfly (Simuliium spp.)and biting midge (Culicoides spp.) species have been suggested as potential vectors. Both blackflies and biting midges are known vectors for many Onchocerca spp. worldwide.
• The domestic dog is considered the primary definitive host for O. lupi. First described in a Russian wolf, O. lupi infection is most likely present in wild canid populations in endemic areas but no studies so far have confirmed this.

Prepatent period and environmental factors

• Currently there is no information available on the time between initial infection and the arrival of adults to the ocular tissues, onset of clinical signs or detectable presence of microfilariae in the skin.
• Developmental time required for ingested microfilariae to develop to the infective stage in the arthropod vector is also unknown but is most likely temperature dependent.
• Blackfly populations are dependent on rivers and other water sources with aquatic vegetation necessary for egg deposition and larval development. Biting midge populations use a variety of moist organic environments for their breeding sites including freshwater swamps or marshes, the shallow edges of ponds streams and rivers, animal manure, and rotting plant materials.
• Sites where canine cases were reported in Portugal and Greece were located close to areas of flowing water where blackfly larvae were found.
• The majority of known infections in dogs, cats and humans in the United States have been primarily in the southwestern states particularly New Mexico as well as Arizona, California, Colorado, Nevada, and Utah. Cases have also been reported in Florida (unknown history) and Minnesota (travel history to Colorado).
• Outside of the U.S. the majority of canine infections have occurred in Greece, but have also been reported in Germany, Hungary, Romania, Switzerland, and Portugal.

Site of infection and pathogenesis

• Onchocerca lupi is a zoonotic filarial nematode found in ocular and adnexal tissues of dogs.
• An aberrant migration in a dog has been reported presenting for severe dyspnea had a nodule in the larynx discovered by cervical and thoracic radiographs and exploratory laryngoscopy.

Diagnosis

• The majority of infected dogs are often asymptomatic especially if development of the adult worms is localized to the retrobulbar space of the eye and not detectable by ophthalmic examination.
• The diagnosis of O. lupi is most often achieved by a detailed ophthalmic evaluation and detection of ocular nodules occurring in the sclera or conjuntiva, subconjuctival threadlike parasites or threadlike fragments, histopathological identification of adult worms, and by identification of microfilariae from skin snip biopsies.
• Dogs originating from or with travel history to the southwestern United States, Europe and the Mediterranean region should be considered at a heightened risk and suspicion for possible infection with Onchocerca lupi, especially if presenting ocular clinical signs.
• A skin snip biopsy originating from the ears, nose, intra-scapular or umbilical regions may allow recovery and identification of microfilariae (100-117.6 μm), from a saline soaked skin biopsy at 37°C or room temp (6-12 hr.), upon microscopy evaluation of the sediment. This method may be used to monitor microfilaremia following treatment.
• In vivo confocal light microscopy has been used to diagnose and monitor subconjunctival O. lupi.
• Ocular ultrasound (10-18MHz) and CT have identified small-mineralized ocular and retro-orbital lesions in 2 asymptomatic dogs positive for the microfilariae of O. lupi in skin snips. One of the two dogs had eosinophilia (1430 cells/μl) and a mild neutrophilia (9724 cells/μl) although infected dogs may have normal blood count results.
• O. lupi is not known to cause false positives on heartworm antigen assays.

Control and prevention

• For prevention, monthly prophylaxis for heartworm is recommended for all dogs but effectiveness against Onchocerca lupi infection is unknown.

Treatment

• If possible surgical excision of periocular nodules and cysts to remove adult worms and fragments is recommended but should not be expected to fully resolve infections. Enucleation may be necessary.
• Surgical removal of worms should accompanied by melarsomine 2.5 mg/kg with 2 doses IM 24 hours apart, ivermectin 50ug/kg subcutaneously, one month after initial treatment, topical antibiotics, and systemic prednisolone (Komnenou et al. 2002, Zarfoss et al. 2005).
• Doxycycline therapy has also been included in the treatment regimen.
• Reoccurrences are common and have occurred ranging from 2 months -33 months post-surgery/medical treatment, so clinical follow-up and monitoring of treatment effectiveness is essential.
• Periodic evaluation of skin snips may be necessary to monitor for clearance of microfilariae following treatment.

Public Health Considerations

• Zoonotic infections in humans have been reported involving the eyes, joints on the limbs, and upper cervical spine masses.
• The risk of infection by O. lupi is possible for individuals originating from or with travel history to the southwestern United States, Mariana Islands, Europe and the Mediterranean region, particularly Greece.

Selected References

• Grácio AJS, Richter J, Komnenou AT, Grácio MA. Onchocerciasis caused by Onchocerca lupi: an emerging zoonotic infection. Systematic review." Parasit Res2015; 114, 7: 2401-2413.
• Otranto D, Giannelli A, Trumble NS, Chavkin M, Kennard G, Latrofa MS, Bowman DD, Dantas-Torres F, Eberhard ML. Clinical case presentation and a review of the literature of canine onchocercosis by Onchocerca lupiin the United States. Parasit & Vectors2015; 8, 1: 89.
• McLean NJ, Newkirk K, Adema CM. Canine ocular onchocerciasis: a retrospective review of the diagnosis, treatment, and outcome of 16 cases in New Mexico (2011–2015). Vet Ophthalmol2017; 20, 4: 349-356.
• Colella V, Lia RP, Paola GD, Cortes H, Cardosa L, Ontronto D, International dog travelling and risk for zoonotic Onchocerca lupi. Transbound Emerg Dis2018; 12: 1-3
• Edelmann ML, Jager M, Espinheira F, Ledbetter EC. In vivo confocal microscopy for detection of subconjunctival Onchocerca lupi infection in a dog. Vet Ophthalmol2017; 1-6
• Franchini D, Gianelli A, Paola GD, Cortes H, Cardosa L, Lia RP, Campbell BE, Dantas-Torres F, Lenoci D, Assad EA, Ricciardi M, Valastro C, Cavaliere L, Bello AD, Ontronto D. Image diagnosis of zoonotic onchocercosis by Onchocerca lupi. Vet Parasit2014;203, 1-2: 91-95.
• Alho AM, Cruz L, Coelho A, Martinho F, Mansinho M, Annoscia G, Lia RP, Gianelli A, Ontronto D, Madeira de Cavalho L. Aberrant laryngeal location of Onchocerca lupiin a dog. Parasit Intl. 2016; 65, 3: 218-220.
• Zarfoss MK, Dubielzig RR, Eberhard ML, Schmidt KS. Canine ocular onchocerciasis in the United State: two new cases and review of the literature. Vet Opthalmol 2005; 8, 1: 51-57
• Komnenou A, Eberhard ML, Kaldrymidou E, Tsalie E, Dessiris A. Subconjunctival filariasis due to Onchocercasp. in dog: report of 23 cases in Greece. Vet Opthalmol 2002; 5, 2: 119-126