Angiostrongylus cantonensis
Adult female worm ofAngiostrongylus cantonensis with characteristic barber-pole appearance (anterior end of worm is to the top). Scale bar is 1 mm.
Scientific classification
Kingdom:	Animalia
Phylum:	Nematoda
Class:	Chromadorea
Order:	Rhabditida
Family:	Angiostrongylidae
Genus:	Angiostrongylus
Species:	A. cantonensis
Binomial name
Angiostrongylus cantonensis (Chen, 1935)[1]
Synonyms[2]
Pulmonema cantonensisChen, 1935

Angiostrongylus cantonensis is anematode (roundworm)parasite that causesangiostrongyliasis, an infection that is the most common cause ofeosinophilic meningitis inSoutheast Asia and thePacific Basin.^[3] The nematode commonly resides in the pulmonary arteries ofrats, giving it the common namerat lungworm.^[4]Snails andslugs are the primary intermediatehosts, wherelarvae develop until they are infectious.

Humans are incidental hosts of this roundworm, and may become infected through ingestion oflarvae in raw or undercooked snails or othervectors, or from contaminated water and vegetables.^[5] The larvae are then transported via the blood to thecentral nervous system, where they are the most common cause of eosinophilic meningitis, a serious condition that can lead to death or permanent brain and nerve damage.^[6] Angiostrongyliasis is an infection of increasing public health importance, asglobalization contributes to the geographic spread of the disease.^[7][8]

First described by Chinese parasitologist Hsin-Tao Chen (1904–1977) in 1935, after examining Cantonese rat specimens,^[1] the nematodeAngiostrongylus cantonensis was identified in thecerebrospinal fluid of a patient with eosinophilic meningitis by Nomura and Lim inTaiwan in 1944. They noted that raw food eaten by the patient may have been contaminated by rats.^{[citation needed]}

A. cantonensis is ahelminth of thephylumNematoda,orderStrongylida, andsuperfamily Metastrongyloidea. Nematodes are roundworms characterized by a tough outercuticle, unsegmented bodies, and a fully developedgastrointestinal tract. The order Strongylida includeshookworms andlungworms. Metastrongyloidea are characterized as 2-cm-long,^[9] slender, threadlike worms that reside in the lungs of the definitive host.^[10]Angiostrongylus costaricensis is a closely related worm that causes intestinal angiostrongyliasis in Central and South America.

Following World War II,A. cantonensis spread throughout Southeast Asia and Western Pacific Islands, includingAustralia,Melanesia,Micronesia, andPolynesia. Cases were soon reported inNew Caledonia, thePhilippines,Rarotonga,Saipan,Sumatra,Taiwan, andTahiti. In the 1960s, even more cases were reported from the region from locations such asCambodia,Guam,Hawaii,Java,Thailand,Sarawak,Vietnam, andVanuatu.^[11]

In 1961, anepidemiological study of eosinophilic meningitis in humans was conducted by Rosen, Laigret, and Bories, who hypothesized that the parasite causing these infections was carried by fish. However, Alicata noted that raw fish was consumed by large numbers of people in Hawaii without apparent consequences, and patients presenting with meningitis symptoms had a history of eating raw snails orprawns in the weeks before presenting with symptoms. This observation, along with epidemiology andautopsy of infected brains, confirmedA. cantonensis infection in humans as the cause of the majority of eosinophilic meningitis cases in Southeast Asia and the Pacific Islands.^[12]

Since then, cases ofA. cantonensis infestations have appeared inAmerican Samoa, Australia,Hong Kong,Bombay,Fiji, Hawaii,Honshu,India,Kyushu,New Britain,Okinawa,Ryukyu Islands,Western Samoa, and most recently mainlandChina. Other sporadic occurrences of the parasite in its rat hosts have been reported inCuba,Egypt,Louisiana,Madagascar,Nigeria, andPuerto Rico.^[11] In 2023 it was detected for the first time in continental Europe in the city ofValencia on the Spanish mainland.^[13]

In 2010, an Australian 19 year old contractedA. cantonensis after consuming a slug on a dare while drunk. This led to him entering a coma for nearly 14 months and becoming paralyzed. This culminated in his death in 2018.^[14]

In 2013,A. cantonensis was confirmed present inFlorida, USA, where its range and prevalence are expanding.^[15] In 2018, a case was found in aNew Yorker who had visited Hawaii.^[16]

In recent years,^[when?] the parasite has been shown to be proliferating at an alarming rate due to modern food-consumption trends and global transportation of food products. Scientists are calling for a more thorough study of the epidemiology ofA. cantonensis, stricter food-safety policies, and the increase of knowledge on how to properly consume products commonly infested by the parasite, such as snails and slugs that act as intermediate hosts or those that act asparatenic hosts, such as fish, frogs, orfreshwater prawns.^[17][18][19]

Ingestion of food items that can be contaminated by the mucus excretions of intermediate or paratenic hosts, such as snails and slugs, or by the feces of rats that act as definitive hosts, can lead to infection ofA. cantonensis.^[20] The most common route of infection ofA. cantonesis in humans is by ingestion of either intermediate or paratenic hosts of thelarvae.^[21] Unwashed fruits and vegetables, especiallyromaine lettuce, can be contaminated with snail and slug mucus or can result in accidental ingestion of these intermediate and paratenic hosts. These items need to be properly washed and handled to prevent accidental ingestion ofA. cantonensis larvae or the larvae-containing hosts.^[22]

The best mechanism of prevention ofA. cantonesis outbreak is to institute an aggressive control of snail and slug population, proper cooking of intermediate and paratenic hosts such as fish, freshwater prawn, frogs,molluscs, and snails along with proper food-handling techniques.^[23] The common prevention techniques for diarrheal illness are very effective in preventingA. cantonensis infection.^[24]

Not much is known about why it targets the brain in humans, but a chemically inducedchemotaxis has been implicated recently.Acetylcholine has been previously reported to enhance motility of this worm vianicotinic acetylcholine receptors.^[25] Experimental assays in animal models are needed to validate achemically induced chemotaxis by use ofanticholinergic drugs to preventcerebral infection following infections byA. cantonesis.^[26]

Intermediate hosts of larvae of forA. cantonensis include:

• Land snails:Thelidomus aspera from Jamaica,^[27][28]Pleurodonte sp. from Jamaica,Sagda sp. from Jamaica,Poteria sp. from Jamaica,^[28]Achatina fulica,^{[29][30][31][32]}Satsuma mercatoria,Acusta despecta,^[31][32]Bradybaena brevispira,^[29]Bradybaena circulus^[31]Bradybaena ravida,Bradybaena similaris,Plectotropis appanata^[29] andParmarion martensi from Okinawa^[31] and Hawaii,^[33]Camaena cicatricosa,Trichochloritis rufopila,Trichochloritis hungerfordianus andCyclophorus spp.^[32]
• Freshwater snails:Pila spp.,^[30]Pomacea canaliculata,^[29][30]Cipangopaludina chinensis,Bellamya aeruginosa andBellamya quadrata^[29] ,Pomacea maculata^[34]
• Slugs:Limax maximus,^[35]Limax flavus^[29]Deroceras laeve,^[29][36]Deroceras reticulatum,^[36]Laevicaulis alte,^[29][31][36]Sarasinula plebeia,^[36]Vaginulus yuxjsjs,^[29]Lehmannia valentiana,^[31]Phiolomycus bilineatus,Macrochlamys loana,Meghimatium bilineatum^[29] and probably other species of slugs.

Definitive hosts ofA. cantonensis include wild rodents, especially the brown rat (Rattus norvegicus) and the black rat (Rattus rattus).^[27]

Paratenic hosts ofA. cantonensis include the predatory land flatwormPlatydemus manokwari and the amphibians,Bufo asiaticus,Rana catesbeiana,Polypedates leucomystax andFejervarya limnocharis.^[31]

In 2004, a captiveyellow-tailed black cockatoo (Calyptorhynchus funereus) and two free-livingtawny frogmouths (Podargus strigoides) suffering neurological symptoms were shown to have the parasite. They were the firstavian hosts discovered for the organism.^[37] In 2018, inMallorca twoNorth African hedgehogs with signs of acuteneurological disease were found to haveA. cantonensis in their brains, one of them with a gravid female.^[38] It was the first report of hedgehogs as hosts ofAngiostrongylus.^[38]

The Hawaiʻi Department of Health states that freshwateropihi can carry the parasite, as well as other aquatic organisms such as prawns, frogs, and water monitor lizards.^[39] House pets may interact withA. cantonensis-carrying animals but this is not well studied. Cats are known to carry and spreadfeline lungworm in rat and snail interactions.^[40]

The presence of parasitic worms burrowed in the neural tissue of the humancentral nervous system (CNS) causes complications. All of the following result in damage to the CNS:^{[citation needed]}

1. Direct mechanical damage to neural tissue from the worms' motion
2. Toxic byproducts such as nitrogenous waste
3. Antigens released by dead and living parasites

Although the clinical disease caused byAngiostrongylus invasion into the CNS is commonly referred to as "eosinophilic meningitis", the actual pathophysiology is of a meningoencephalitis with invasion not just of themeninges, or superficial lining of the brain, but also deeper brain tissue. Initial invasion through the lining of the brain, the meninges, may cause a typical inflammation of the meninges and a classic meningitis picture of headache, stiff neck, and often fever. The parasites subsequently invade deeper into the brain tissue, causing specific localizingneurological symptoms depending on where in the brainparenchyma they migrate. Neurologic findings and symptoms wax and wane as initial damage is done by the physical in-migration of the worms and secondary damage is done by the inflammatory response to the presence of dead and dying worms. This inflammation can lead in the short term to paralysis, bladder dysfunction, visual disturbance, and coma and in the long term to permanent nerve damage, mental retardation, nerve damage, permanent brain damage, or death.^[41]

Eosinophilic meningitis is commonly defined by the increased number ofeosinophils in thecerebrospinal fluid (CSF). In most cases, eosinophil levels rise to 10 or more eosinophils per μl in the CSF, accounting for at least 10% of the total CSFleukocyte (white blood cell) count.^[42] The chemical analysis of the CSF typically resembles the findings in "aseptic meningitis" with slightly elevated protein levels, normal glucose levels, and negative bacterial cultures. Presence of a significantly decreased glucose on CSF analysis is an indicator of severemeningoencephalitis and may indicate a poormedical outcome. Initial CSF analysis early in the disease process may occasionally show no increase of eosinophils, only to have classical increases in eosinophils in subsequent CSF analysis. Caution should be advised in using eosinophilic meningitis as the only criterion for diagnosing angiostrongylus infestation in someone with classic symptoms, as the disease evolves with the migration of the worms into the CNS.^{[citation needed]}

Eosinophils are specialized white blood cells of thegranulocytic cell line, which contain granules in theircytoplasm. These granules contain proteins that are toxic to parasites. When these granules degranulate, or break down, chemicals are released that combat parasites such asA. cantonensis. Eosinophils, which are located throughout the body, are guided to sites of inflammation bychemokines when the body is infested with parasites such asA. cantonensis. Once at the site of inflammation, type 2 cytokines are released fromhelper T cells, which communicate with the eosinophils, signaling them to activate. Once activated, eosinophils can begin the process ofdegranulation, releasing their toxicproteins in the fight against the foreign parasite.^{[citation needed]}

According to a groupcase study, the most common symptoms in mild eosinophilic meningitis tend to be headache (with 100% of people in the study suffering from this symptom),photophobia or visual disturbance (92%), neck stiffness (83%), fatigue (83%),hyperesthesias (75%), vomiting (67%), andparesthesias (50%).^[43][24]Incubation period is often 3 weeks, but can be 3–36 days^[11] and even 80 days.^[44]

Possible clinicalsigns andsymptoms of mild and severe eosinophilic meningitis are:

• Fever is often minor or absent, but the presence of high fever suggests severe disease.^[43]
• Headaches are progressive and severe,^[43] a bitemporal character in the frontal oroccipital lobe.^[11]
• Meningismus – neck stiffness^[43]
• Photophobia – sensitivity to light^[43]
• Muscle weakness and fatigue^[11][44]
• Nausea with or without vomiting^[11][43]
• Paresthesias – tingling, prickling, or numbing of skin, may last for several weeks or months^[11]
• Hyperesthesia – severe sensitivity to touch; may last for several weeks or months^[43]
• Radiculitis – pain irradiated along certain areas of skin^[43]
• Bladder dysfunction withurinary retention^[45]
• Constipation^[45]
• Brudziński's sign^[44]
• Vertigo
• Blindness
• Paralysis localized to one area; e.g., paralysis ofextraocular muscles andfacial palsy^[44]
• General paralysis (flaccid)^[11] often ascending in nature starting with the feet and progressing upwards to involve the entire body
• Coma^[43]
• Death^[43]

The severity and clinical course ofAngiostrongylus disease depends significantly on the ingested load of third-stagelarvae,^[46] creating great variability from case to case, making clinical trials difficult to design, and effectiveness of treatments difficult to discern. Typical conservative medical management includinganalgesics andsedatives provide minimal relief for the headaches andhyperesthesias. Removing cerebrospinal fluid at regular 3- to 7-day intervals is the only proven method of significantly reducingintracranial pressure and can be used for symptomatic treatment of headaches.^[47] This process may be repeated until improvement is shown.^[42] There is growing evidence of moderate quality that suggestscorticosteroid therapy usingprednisolone^[48] ordexamethasone^[49] has beneficial effect in treating theCNS symptoms related toA. cantonensis infections.^[50][51] Although early research did not show treatment withantihelminthic agents (parasite-killing drugs) such asthiobendazole oralbendazole effective in improving the clinical course of the illness,^[52][43] a number of recent^[when?] studies from Thailand and China show that the combination ofglucocorticoids and antihelminthics is safe and decreases the duration of headaches and the number of patients who had significant headache.^{[49][48][53][54]} Although the addition of antihelminthic agents for management ofA. cantonensis infection has a theoretical risk of precipitating a neurologic crisis by releasing an overwhelming load ofantigens through simultaneous death of the larvae,^[47] no study has shown this to exist in the clinical setting.^{[50][49][54][48]} Additionally, the failure to kill parasites before they attempt to migrate out of the CNS increases the risk of mechanical damage by migrating larvae. Although combination therapy using albendazole and prednisolone has no significant advantage compared to treatment using prednisolone alone in mild cases,^[55] the treatment with antihelminthics is demonstrably safe and may have significant benefit for patients with high parasite loads at risk for permanent disability or death.^[41]

The diagnosis of disease caused byA. cantonensis infestation is often difficult and relies heavily on the history of a likely ingestion of a commonly infested host and the presence of typical features of the disease. The presumptive diagnosis is particularly strong when eosinophilic meningoencephalitis can be confirmed. The diagnosis of eosinophilic meningitis can be arrived at through detection of elevated cranial pressure and increased numbers of eosinophils. The diagnosis of the cause of eosinophilic meningitis and the presence ofA. cantonensis is remarkably more difficult. Aspinal tap, or a sample of CSF, must be taken to search forA. cantonensis worms or larvae.A. cantonensis is undetectable in the CSF of more than half of the infected individuals. Current methods of detecting specific antigens associated withA. cantonensis are also unreliable. Consequently, alternative approaches to detect antigen-antibody reactions are being explored, such asimmuno-PCR.^[56] A rapid dot-blotELISA test is also available for quick, effective, and economical on-site diagnosis ofA. cantonensis.^[57]

Wikimedia Commons has media related toAngiostrongylus cantonensis.

"Angiostrongylus".CDC.gov.Centers for Disease Control and Prevention. 2015-12-28. Retrieved2017-04-04.

• "DPDx - Angiostrongyliasis".CDC. 2016-10-17. Retrieved2017-04-04. Tabs for Parasite Biology, Image Gallery, Laboratory Diagnosis, and Treatment Information.
• Angiostrongylus+cantonensis at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
• Sydney Morning Herald story of human infection, Example ofAngiostrongylus cantonensis human infection: Hard to swallow: slug-eating dare causes rare disease
• Angiostronglyus cantonensis on theUF /IFAS Featured Creatures website.

• Strongylida
• Parasitic nematodes of mammals
• Rodent-carried diseases
• Parasites of rodents
• Zoonotic parasitic diseases
• Global health
• Nematodes described in 1935

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