Angiostrongyliasis, Neural

[Angiostrongylus cantonensis]

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Causal Agent

The nematode (roundworm) Angiostrongylus (=Parastrongylus) cantonensis, also called the rat lungworm, is a common cause of human eosinophilic meningitis (neural angiostrongyliasis) and occasionally ocular disease.

Angiostrongylus costaricensis is the causal agent of abdominal angiostrongyliasis and is discussed here.

Life Cycle

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Adult worms of A. cantonensis live in the pulmonary arteries and right ventricle of the normal definitive host

. The females lay eggs that hatch in the terminal branches of the pulmonary arteries, yielding first-stage larvae. The first-stage larvae migrate to the pharynx, are swallowed, and passed in the feces. They penetrate or are ingested by a gastropod intermediate host

. After two molts, third-stage larvae are produced

which are infective to mammalian hosts. When the infected gastropod is ingested by the definitive host, the third-stage larvae migrate to the brain where they develop into young adults

. The young adults return to the venous system and then the pulmonary arteries where they become sexually mature. Of note, various animals act as paratenic (transport) hosts: after ingesting the infected snails, they carry the third-stage larvae which can resume their development when the paratenic host is ingested by a definitive host. Humans can acquire the infection by eating raw or undercooked snails or slugs infected with the parasite; they may also acquire the infection by eating raw produce that contains a small snail or slug, or part of one

. There is some question whether or not larvae can exit the infected gastropods in slime (which may be infective to humans if ingested, for example, on produce). Infection may also be acquired by ingestion of invertebrate paratenic hosts containing L3 larvae (e.g. crabs, freshwater shrimp). In humans, larvae migrate to the brain, or rarely to the lungs, where the worms ultimately die

. Larvae may develop to fourth or fifth stage in the human host, but seem to be incapable of maturing fully.

Learn more about Angiostrongylus cantonensis in this new motion graphic video.

Hosts

A. cantonensis is known to use multiple rat species as definitive hosts, including black rats (Rattus rattus), brown rats, (Rattus norvegicus), and cotton rats (Sigmodon hispidus). Gastropod (snail and slug) intermediate hosts are numerous and include Achatina spp., Biomphlalaria spp., Bulinus spp., Lymnaea spp., Pomaecea spp., and more. Apart from humans, aberrant infections have occurred in several species of wild and domestic mammals and birds.

Geographic Distribution

Most cases of A. cantonensis-associated eosinophilic meningitis originate from Southeast Asia and Pacific Islands. The parasite has also been reported from Africa, the Caribbean, Australia, Hawaii, and recently the southern United States.

Clinical Presentation

The most notable manifestation of A. cantonensis infection is eosinophilic meningitis caused by the presence of larvae in the brain and resultant local host reactions. Somatic symptoms (e.g. headache, fever, malaise) as well as varying degrees of neurological dysfunction are usually noted. A. cantonensis infection may occasionally prove fatal. Ocular angiostrongyliasis is associated with uveitis, blurred vision, and a substantial loss of visual acuity.

Angiostrongylus sp. male worms.

Figure A: Angiostrongylus sp. male worm, approximately 4.25 mm in length, recovered from vitreous humor of a human patient. The worm is most likely A. cantonensis based on the patient's geographic location.

Figure D: Angiostrongylus adult worm recovered from vitreous humor of a human patient. Males possess a small copulatory bursa (arrow) supported by bursal rays (dart).. The worm is most likely A. cantonensis based on the patient's geographic location.

Figure B: Angiostrongylus worm. Note the very long spicules (black arrows), one of the indications that this is a male worm.

Figure E: Same specimen as in Figure D but in a different focal plane.

Figure C: Higher magnification of the worm in Figure B.

A. cantonensis subadults (L5)

Figure A: Subadult A. cantonensis male (~4 mm long) from the CSF of a human patient. Note the presence of a bursa on the posterior end.

Figure B: Closer view of the posterior end of the male shown in Figure A, showing the spicules (arrow) and bursa. The long spicules aid in distinguishing A. cantonensis from most other Angiostrongylus spp.

Figure C: Subadult A. cantonensis female (~4.2 mm long) from the same case.

Figure D: Closer view of the posterior of the female shown in Figure C. The vulva (arrow) and anus (dart) are indicated.

A. cantonensis third-stage larvae (L3).

L3 larvae are infective to humans, who serve as incidental hosts. They are around 0.5 mm long, possess a pointed terminal projection on the end of the tail, and may be encased in cuticle (exuviae) molted from previous stages. The following photographs show L3 larvae derived from slug tissues.

Figure A: Angiostrongylus cantonensis third stage (L3), infective larva recovered from a slug. Image captured under differential interference contrast (DIC) microscopy.

Figure B: A. cantonensis (L3), infective larvae recovered from a slug. Image captured under DIC microscopy.

Figure C: Higher magnification of Image B. Note the terminal projection on the tip of the tail which is characteristic of A. cantonensis.

A. cantonensis larvae recovered from slugs.

Figure A: Angiostrongylus cantonensis third stage (L3), infective larva, in a wet mount, recovered from a slug. Note the terminal projection on the tip of the tail which is characteristic of A. cantonensis.

Figure B: A. cantonensis L3 infective larva in wet mount, recovered from slug tissue. The arrow indicates the sclerotized rhabdions (small chitinous rods) on the anterior extremity.

Figure C: A. cantonensis L3 infective larva in wet mount, recovered from slug tissue

Clinical and Morphologic Diagnosis

In eosinophilic meningitis with A. cantonensis, the cerebrospinal fluid (CSF) is abnormal (elevated pressure, proteins, and leukocytes; eosinophilia). On rare occasions, larvae have been found in the CSF or in sections of brain tissue.

Molecular Diagnosis

The CDC offers a real-time PCR assay for the specific detection of A. cantonensis in human CSF specimens. The CSF should be kept cold (ice packs) and shipped to CDC as soon as possible; alternatively it can be kept frozen until shipment is arranged. Shipment on dry ice is optional. Recommended volume of CSF is at least 2 mL. Volumes less than 1 mL may lead to reduced test sensitivity.

Diagnostic References:

Qvarnstrom Y, da Silva AQA, Teem JL, Hollingsworth R, Bishop H, Graeff-Teixeira C, and da Silva AJ: Improved Molecular Detection of Angiostrongylus cantonensis in Mollusks and Other Environmental Samples with a Species-Specific Internal Transcribed Spacer 1-Based TaqMan Assay. Appl. Envir. Microbiol.; 2010; 76: 5287 – 5289.

Qvarnstrom Y, Sullivan JJ, Bishop HS, Hollingsworth R, da Silva AJ: PCR-based detection of Angiostrongylus cantonensis in tissue and mucus secretions from molluscan hosts. Appl. Environ. Microbiol.; 2007; 73:1415-1419.

Eamsobhanaa P, Limb PE, Solano G, Zhange H, Ganf X, Yongc HS: Molecular differentiation of Angiostrongylus taxa (Nematoda: Angiostrongylidae) by cytochrome c oxidase subunit I (COI) gene sequences. Acta Tropica; 2010; 116: 152–156.

Laboratory Safety

Observe standard universal precautions for handling CSF and other bodily fluids.