Case Report: A Human Case of Onchocerca lupi Mimicking Nodular Scleritis

ABSTRACT.

We report a case of human ocular onchocerciasis by zoonotic Onchocerca lupi presenting as nodular scleritis. Molecular analyses were used to confirm diagnosis at species level. In addition to few existing reports of human infection by O. lupi in Turkey, this case further suggests that the pathogen might be more common than previously reported, thus requiring further attention and investigations.

INTRODUCTION

Onchocerca lupi is a filarioid nematode primarily infecting dogs and cats in southern and central Europe, and the United States^1–3 However, its epidemiology is far from being understood because of the lack of information on its insect vector species.⁴ Clinical evidence suggests that when O. lupi causes ocular disease, it could invade extra and intraocular tissues.^1,5,6 After the first report of human infection by O. lupi in Turkey,⁷ the pathogen has not been diagnosed in canine natural reservoirs. Screening on more than 100 sheltered animals from Izmir city gave negative results (Otranto, personal communication). Herein, we describe a case of ocular O. lupi infection mimicking as nodular scleritis, also invading lateral rectus muscle. We also report a new geographical location for the parasite in human and further suggesting the presence of this filarioid nematode in the canine population of Turkey.

CASE REPORT

A 20-year-old female presented to the uveitis clinic with a 4-year history of hyperemic, localized swelling at the temporal bulbar conjunctiva of the left eye. The patient did not report any history of trauma or insect bite on the ocular or periocular region. She was living in a rural area (Kırıkkale, Balliseyh 39°55′N 33°43′E, 70 km east to the capital Ankara) cohabiting with dogs, cats, and livestock. She received periodic topical steroid treatments for the swelling and hyperemia without significant improvement. Her detailed surgical and medical history were otherwise unremarkable.

Ocular examination was normal except a slightly elevated, localized episcleral mass measuring approximately 6 × 5 mm in diameter, located at the temporal bulbar conjunctiva of the patient’s left eye (Figure 1A). There was overlying minimal episcleral and conjunctival hyperemia. The nodule was partially mobile and painless on gentile palpation with cotton tip applicator. The anterior margin of the mass was located 6.5 mm away from the limbus. The blood work was largely nonrevealing with slightly elevated erythrocyte sedimentation rate.

Figure 1.

(A) Episcleral nodular mass (white arrow) located at the temporal bulbar conjunctiva of patient’s left eye. (B) Mass found to be confined within a fibrous sheath and adherent to the lateral rectus muscle (black arrow) and its capsule. (C) Parasite was found to be tangled around and under the lateral rectus muscle forming a glomus-like appearance. (D) Although the coiled parasite was loosened from the rectus muscle with the help of a tying forceps, it could not be untangled completely. This figure appears in color at www.ajtmh.org.

A decision was taken to excise the mass surgically under general anesthesia. Before excision, careful exploration of the subconjunctival space and anterior orbit was performed. The mass was confined within a fibrous sheath adherent to the lateral rectus muscle and its capsule (Figure 1B). Tenon’s fascia, fibrous sheath, and muscle capsule were dissected. During the surgical exploration, a worm-like structure was found tangled around and under the lateral rectus muscle forming a glomus-like appearance (Figure 1C). There was no evidence of scleral invasion. Efforts were made to untangle the parasite with the help of tying forceps and to remove it completely (Figure 1D), nonetheless the parasite was withdrawn in smaller segments. Samples were sent for pathological, parasitological, and molecular analyses. Patient’s IgE levels were checked immediately after surgery and were found to be normal (12.9 IU/mL).

The specimen was preserved in 10% formaldehyde and 70% ethanol for histopathological and molecular processing, respectively. Following routine fixation with neutral formalin, and tissue processing, the whole tissue was embedded in paraffin and sectioned at 4 µm. The sections were then stained with hematoxylin and eosin and Masson’s trichrome stains, which revealed some distinct morphologic features of genus Onchocerca, such as a thick cuticle composed of external ridges and internal transverse striae with a ratio of 2:1 typical of O. lupi (Figure 2). However, because the nematode’s internal organs collapsed, some other distinctive characters (e.g., length of esophagus and distances of vulva from the anterior end) could not be studied. Therefore, the specimen was sent to the Unit of Parasitology of the Department of Veterinary Medicine, University of Bari, Italy, for species identification. The specimen was analyzed molecularly after genomic DNA extraction and amplification of the mitochondrial 12S rRNA gene fragment (304 bp) as described elsewhere.⁸ BLAST analysis (http://blast.ncbi.nlm.nih.gov/Blast.cgi) of the sequence obtained showed a nucleotide identity of 100% with those of other O. lupi retrieved in humans from Germany, Turkey, and Iran (KP347443, HQ207645, and JN863696) available in GenBank. The morphological and molecular identification was also supported by the phylogram obtained by the phylogenetic analysis carried out using the Maximum Likelihood method by MEGA5 software,⁹ including the mitochondrial sequence herein obtained within the clade of other homologous sequences of O. lupi obtained from GenBank database (Supplemental Figure). The 12S rRNA sequence obtained was deposited in GenBank under the accession number MT386334.

Figure 2.

(A and B) Hematoxylin and eosin stain showing thick cuticle of the parasite. It is composed of external ridges (black arrows) and internal transverse striae (yellow arrows) with a ratio of 2 to 1. (C) Masson’s trichrome stain demonstrating different sections of the parasite with its cuticle and some collapsed internal organs. This figure appears in color at www.ajtmh.org.

The patient was treated with topical 0.5% moxifloxacin, 0.1% dexamethasone, oral ivermectin 150 mg/kg/day and doxycycline 200 mg/day, after surgery. Episcleral hyperemia persisted for 2–3 months eventually healing with a fine fibrovascular tissue at 9 months follow-up.

DISCUSSION

Onchocerca lupi, a zoonotic filarioid nematode, is a parasite of dogs in parts of Europe and United States. In humans, the first confirmed infection of O. lupi was reported in 2011 from Turkey as a subconjunctival lesion.⁷ Subsequently, few cases that were reported earlier as a nonspecific ocular onchocerciasis, were reevaluated and reclassified as cases of suspected ocular O. lupi based on the newly established diagnostic features of the parasite.⁸ Furthermore, the current molecular and phylogenetic data suggest that the genetic makeup of O. lupi specimen infecting human could be more conserved within this host, because identical 12S rRNA sequence were retrieved when comparing with those of the parasites found in patients from different geographical areas (i.e., Germany, Iran, and Turkey).^7,10,11

Although many Onchocerca spp. are common in tropical-subtropical areas, the current case underlines the fact that human transmission of zoonotic O. lupi may occur also in other geographical location. Previous cases of ocular O. lupi were reported mostly from coastal areas in Turkey that are generally warm and humid.^7,8,12 The first reported case was from Istanbul (Turkey, 41°1′N, 28°57′E) of a patient who had never traveled abroad except to Antalya (Turkey, 39°53′N 30°42′E).⁷ Istanbul, as a result of its location in a transitional climatic zone can experience Mediterranean or humid subtropical climates. Antalya is a Mediterranean city with a hot-summer climate.¹³ The second case lived in Edirne (41°40′N, 26°34′E; about 50 m above sea level) and in Istanbul and had never been abroad or in other areas of Turkey.⁸ Edirne has a humid subtropical and hot-summer Mediterranean climate as well.^8,13 The third reported case was a farmer from a village near Izmir (38°25′N, 27°09′E), which is also an Aegean coastal city having the similar climate described earlier.¹³ Interestingly, the case reported herein was from a central city (Kırıkkale 39°55′N 33°43′E) in Turkey, which has a cold semiarid climate.¹³ It is important to note that the parasite cannot spread directly from animals to human, as it needs to complete part of its life cycle in an intermediate host, whose identity remains yet to be revealed. Identifying specific areas of infected mammalian species and vectors (e.g., black flies and biting midges) will increase our understanding of the life cycle of O. lupi, and thus help to create specific public policies and advocate further research targeting both hosts and vectors to reduce the risk of infection in humans.

CONCLUSION

Onchocerca lupi is an emerging filarioid nematode that may present as a subconjunctival hyperemic nodule mimicking nodular scleritis. It may also involve the rectus muscle. Molecular analyses are useful to confirm diagnosis at species level as well as to establish which sequence type of O. lupi could be shared among humans, hosts, and potential vectors. However, this confirmed human case in Turkey suggests that the pathogen might be more common than previously reported, thus requiring further attention and investigations.

Note: Supplemental figure appears at www.ajtmh.org.