Update on the treatment and prevention of ocular thelaziosis (Thelazia callipaeda) in naturally infected dogs from Spain

Highlights

• Appropriate management of Thelazia callipaeda is being widely promoted in Europe.

• Treatment of infected pets is key to reducing prevalence and public health impacts.

• Monthly prophylactic treatment is essential to control T. callipaeda infection.

Abstract

This study examines the therapeutic and year-round prophylactic efficacy of different formulations used in dogs in three Spanish areas where canine thelaziosis is endemic. The study was conducted as a Good Clinical Practice, multicentre, randomised field study in privately owned outdoor dogs naturally infected with Thelazia callipaeda. The active pharmaceutical ingredients tested were: an oral formulation of milbemycin oxime 12.5 mg combined with praziquantel 125 mg (A), a subcutaneous sustained-release formulation of moxidectin 10 g (B), a moxidectin 2.5% weight/volume (w/v) spot-on formulation combined with imidacloprid 10% w/v (C), and an eye drop formulation (6 µg) of ivermectin 10 mg/ml diluted 10% in propylene glycol (D). Infected dogs were randomly allocated to treatment Groups A, B, C and D. Dogs testing negative for T. callipaeda inspection in two visits (Day 7/Day 14 and D30) were enrolled in the prophylaxis trial and reallocated to the corresponding study group (A, B, C or D). Treatment efficacy ranged from 70.4% recorded in Group A 1 week after treatment, to 100% recorded in Group C on Day 30 and in Group B on Day 60. Treatment was more efficacious in Group D (85.7% 1 week after treatment) than A, but was never 100% efficacious as in Groups B and C. Year-round prophylactic efficacy was 83.3% in Group A, 100% in Group B, 93.5% in Group C and 87.5% in Group D. In conclusion, products containing moxidectin were highly efficacious both in treating and preventing canine thelaziosis. Milbemycin also emerged as a good option. However, the off-label use of topical or subcutaneous ivermectin should be avoided due to possible adverse reactions such as pruritus, irritation or redness. In endemic areas, monthly prophylaxis to limit the spread of T. callipaeda to new areas across Europe and reduce zoonotic risks is essential.

Introduction

The nematode Thelazia callipaeda (Spirurida: Thelaziidae) infests the eyes of dogs and cats as well as many other mammals, including humans. In their hosts, adult eyeworms reside under the eyelid, causing subclinical infection or ocular signs such as epiphora, photophobia, conjunctivitis, keratitis and ulcers (Anderson, 2000, Otranto and Traversa, 2005). In Europe, the vector and intermediate host of this nematode is the male drosophilid fly Phortica variegata (Diptera, Drosophilidae), which displays zoophilic behaviour by feeding on the host's lachrymal secretions (Otranto et al., 2006).

Due to its original distribution in eastern Asian countries, T. callipaeda was known as the “Oriental eyeworm” (Bhaibulaya et al., 1970, Shi et al., 1988, Anderson, 2000, Shen et al., 2006). This term is no longer appropriate because cases of T. callipaeda infection have been described in dogs and/or cats in many European countries including Italy, France, Germany, Switzerland, Spain, Portugal, Belgium, Bosnia and Herzegovina, Croatia, Serbia, Romania, Greece, Bulgaria, Hungary, Slovakia, United Kingdom, Turkey, Austria, Czech Republic, Republic of Moldova, and Andorra (Colella et al., 2016, do Vale et al., 2019, Dumitrache et al., 2019, Hofmannová et al., 2019, Marino et al., 2020).

In humans, thelaziosis has been reported in Italy and France (Otranto and Dutto, 2008), Spain (Fuentes et al., 2012, López Medranoet al., 2015, Deltell et al., 2019) and, more recently, in Croatia, Serbia and Germany (Paradžik et al., 2016, Tasić-Otašević et al., 2016, Dolff et al., 2020), and has accordingly been described as a public health concern (Otranto and Dutto, 2008).

The therapeutic and prophylactic efficacy of different drugs against canine thelaziosis has been a topic of recent investigation. Treatment is based on removing nematodes directly from the eyes of affected dogs (after local anaesthesia, e.g. oxybuprocaine hydrochloride and tetracaine hydrochloride) and then applying macrocyclic lactones (Nolan and Lok, 2012) as eye drops (Lia et al., 2004, Rossi et al., 2007), spot-ons (Bianciardi and Otranto, 2005, Otranto et al., 2016), or as oral (Fudge et al., 2007, Motta et al., 2012, Otranto et al., 2016) or injectable formulations (Rossi et al., 2007).

Moxidectin and milbemycin oxime are the only molecules registered in Europe for the treatment of canine thelaziosis (Motta et al., 2012, Otranto et al., 2016, Otranto et al., 2019). Monthly treatment with milbemycin oxime at the dose recommended for heartworm disease prophylaxis is efficacious for the treatment and prophylaxis of T. callipaeda (Ferroglio et al., 2008). In effect, this active principle has recently been approved to prevent infection with the parasite (Lebon et al., 2019). The agent is used orally at 0.5 mg/kg, and two doses given 1 week apart are recommended. The monthly application of a spot-on formulation of moxidectin 2.5% and imidacloprid 10% has also proved highly efficacious in preventing T. callipaeda infection (Lechat et al., 2015). However, to date, there have been few comparative studies on the therapeutic and prophylactic efficacy of drugs used against canine thelaziosis. To reduce the risk of human infection it is, nevertheless, mandatory that we adequately control ocular thelaziosis in animals that live in endemic areas.

The aim of the present study was to compare the therapeutic and prophylactic actions of several active ingredients in different formulations used all year round in dogs in three Spanish regions endemic for canine thelaziosis.