Commentary: Angiostrongylus cantonensis in anterior chamber.

Angiostrongylus cantonensis[1] is a nematode (roundworm) worm belonging to the phylum Nematoda, order Strongylida, and superfamily Metastrongyloidea, nicknamed as rat lungworm; Nomura and Lim in Taiwan called this parasite as Haemostrongylus ratti in 1944. Its life cycle was described by Mackerass and Sanders in 1955. But as early as 1935, Chen from China described the worm from the bronchial tree of the rats.

Morphologically, it is a delicate filiform worm, with a length of 16–25 mm and a diameter of 0.26–0.36 mm with the female longer than males. The rodent is the definite host. Humans, the accidental host, are infected by eating inadequately cooked intermediate hosts (slugs, snails, crabs) containing third-stage larvae (L3) or vegetables contaminated by larvae. The portal of entry into the orbit is between the optic nerve and sheath, through the cribriform plate from the brain by the fifth stage of larva as postulated by Kanchanaranya et al.[2] It can enter into the anterior chamber through the limbus as well. It commonly causes helminthic infection in the Southeast Asian countries. However, it assumes public health significance because of modern age travel and migration.[3]

In human beings, the clinical manifestations are protean. It ranges from meningoencephalitis, eosinophilic meningitis, and diverse ocular manifestations. The ocular features are optic neuritis, blepharospasm, uveitis, macular edema, retinal edema, necrotic retinitis, panophthalmitis, papilledema, and optic nerve compression. Punyagupta et al. estimated that among typical eosinophilic meningitis, 16% of patients had visual impairment, whereas 12% had an optic disc abnormality like papilledema or atrophy. However, the low number of ocular cases reported from countries other than Taiwan, China, could be due to under recognition of the parasite or an intraspecies variation of the pathogenicity[4] of L3 in the host.

The diagnostic criteria[5] formulated by Chinese Ministry of health in 2006 stratified Strongyloidosis into three subgroups of suspected, clinically diagnosed, and parasitologically diagnosed based on the following features: [1] eating history; [2] clinical features (headache, nausea, vomiting, visual disturbances, photophobia, nuchal rigidity, hyperesthesia, paresthesia); [3] elevated eosinophil count (>500 cell/μl) in peripheral blood; [4] elevated eosinophil count (>10 cell/μl) in cerebrospinal fluid (CSF); [5] seropositivity for specific Angiostrongylus cantonensis or corresponding antibody; and [6] and presence of A. cantonensis in CSF, anterior chamber, vitreous cavity, and subretinal space, presence of larvae in sections of brain/spinal cord, or presence of the worms in pulmonary arteries or the heart. Diagnosis is mainly clinical as only 10% of cases of eosinophilic meningitis[6] have ocular involvement. Laboratory methods like ELISA, western blotting, and use of specific monoclonal antibodies against the parasite (29, 31, and 32 kD] and Ig G4 are supportive[7] and are sparsely available with varying sensitivity. What is very practical is evaluation of elevated peripheral eosinophilia and absolute eosinophilic count.

Conversely, majority of ocular cases of ocular Angiostrongylosis are not associated with central nervous system (CNS) infections. If both the eye and CNS infections are infected simultaneously, then CNS infection should precede the eye presentations based on the life cycle. The clinician should keep an eye on the differentials of eosinophilic meningitis[7] as well.

Apart from the migration of the parasite in the anterior/posterior segment of the eye with the retinal epithelial tracts, the clinician should look for subretinal tracks, retinal edema, macular edema, and a pale disc due to optic neuritis. The postulated mechanisms for optic neuritis are the raised intracranial pressures or the direct invasion. For the clinician, the investigations to document/suspect optic neuritis in appropriate clinical scenarios include the undilated pupillometry for evaluation of relative afferent pupillary defect as well as dilated fundoscopy. Ancillary investigations like electroretinogram (ERG) and visually evoked potential (VEP) can be applied as when needed.

In real-time scenarios when a clinician encounters a live parasite in anterior or posterior segment, the real challenge is to prevent the migration of the worm to the systems. Direct argon, Yag, Diode laser-assisted killing of the worm is the lucid definitive gold standard in the treatment of this helminthic zoonosis. When the worm is in anterior segment, the practical tip such as application of 4% pilocarpine eye drops is useful to not only constrict the pupil but also to anaesthetize the worm, thanks to its organophosphorous compound moiety. This can aid immediate delicate surgical removal of the worm with varied techniques and subject it for morphological characterization of the worm. However, few reports of Yag laser-assisted killing/immobilization of the worm in the anterior segment may help to avoid the migration when surgery is not feasible in peripheral centers. This can be followed by surgical removal of the worms/worm particles and sending it to appropriate laboratories.

Traditionally, Angiostrongylosis can be easily identified by the microbiologists based on its morphological features. The closer differentials[8] to be considered are Loa loa, Toxocara, Ascaris Gnathostoma, Onchocerca, Brugia/Wucheraria, and Dirofilaria. In particular, sex differentiation of the worm can be done by the presence of small delicate bursa at the terminal end of males and blunt ended subterminal anal pore in females. Additional snail examination techniques by “lung examination” method by Liu et al.[9] and artificial digestion method in batches are worth a consideration from public health perspective.

Speciating the parasite[10] had blossomed to the next level using the polymerase chain reaction techniques from worm particles. The taxonomical identification of nematode can be done even with small fragments of the nematode using DNA barcoding of cox-1 and 12 S markers. In a practical situation when exact identification is dicey, the novel techniques like delineation of Molecular Operational Taxonomical units (MOUT) can help to identify new species as well. In the age of advanced molecular diagnostics, the sequences are compared with those available in the GenBank database[11] by a technique called Basic Local Alignment Search Tool (BLAST).

Topical steroids, cycloplegics, and appropriate antiglaucoma medications are indicated for the incited inflammation and its sequel. When optic neuritis is suspected, parenteral steroids are given although prognosis is poor. The visual recovery depends on initial visual acuity and time of presentation. Oral and topical steroids help in preventing further visual deterioration incited by laser and surgical procedures. With no specific antihelminthics against A. cantonensis, the penetration of Albendazole into eye is doubtful. It can paradoxically incite the inflammation before removing the parasite. However, it can be a consideration following removal of worm under the cover of steroids for potential systemic deworming and shortening the sequelae as suggested by their usage in the endemic mainland. But to date, there are no randomized studies done to prove this practical point of view!

From the public health perspective, preventive strategies should focus on the corresponding sources in the appropriate geographical areas. Its life cycle involves diverse edible intermediate host mollusks and paratenic hosts. Consumption of raw or undercooked snails is implicated in Southeast Asia. In the Caribbean, the possible sources are contaminated vegetables and condiments. In India and Sri Lanka, snails and monitor lizard are the main sources of infection. Freshwater shrimps, fish, and crabs are the suspected infective sources in the Pacific Isles.[5] Truly uveitis varies with the geography!