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Angiostrongyliasis

Angiostrongyliasis is a zoonotic parasitic caused by nematodes of the genus Angiostrongylus, most commonly A. cantonensis (the rat lungworm), which leads to neuroangiostrongyliasis characterized by eosinophilic meningitis, and A. costaricensis, which causes abdominal angiostrongyliasis involving the intestines. Humans serve as accidental dead-end hosts, acquiring the primarily through ingestion of larvae in raw or undercooked intermediate hosts like s and slugs, or contaminated produce and paratenic hosts such as freshwater prawns, crabs, or frogs. The spread is aided by invasive intermediate hosts such as the giant African (Lissachatina fulica). The disease is endemic in and the Pacific Basin for A. cantonensis, with the parasite spreading to and emerging human cases in the and the , while A. costaricensis is mainly reported in Central and . Several thousand cases have been reported worldwide since its first description in 1945, often linked to culinary practices involving raw mollusks, and the poses a concern due to its potential for severe neurological complications. The of Angiostrongylus involves rats as definitive hosts, where reside in the pulmonary arteries (A. cantonensis) or mesenteric arteries (A. costaricensis), producing larvae that are shed in feces and ingested by mollusks to develop into infective third-stage larvae. In humans, ingested larvae migrate to the for A. cantonensis, eliciting an intense inflammatory response that causes tissue damage, or to the for A. costaricensis, leading to intestinal wall and potential . is facilitated by environmental factors like humid climates favoring mollusk populations, and outbreaks have been associated with contaminated salads or direct consumption of slugs in regions like and . Clinical manifestations of neuroangiostrongyliasis typically emerge 1 to 6 weeks post-exposure and include severe (affecting over 90% of patients), , paresthesias, low-grade fever, , and , with rare progression to seizures, cranial nerve palsies, or coma in severe cases. Abdominal angiostrongyliasis presents with right lower quadrant pain mimicking , anorexia, and , predominantly in children under 10 years old. Ocular involvement occurs in about 1% of A. cantonensis cases, potentially causing vision loss due to larval migration into the eye. Diagnosis relies on epidemiological history, analysis showing (>10% ), and confirmatory tests like or for A. cantonensis, while A. costaricensis often requires . Management is primarily supportive, as anthelmintic drugs like may worsen inflammation by killing larvae and are used cautiously alongside corticosteroids such as prednisolone to mitigate responses. For severe neuroangiostrongyliasis, repeated punctures can alleviate , and surgical intervention may be needed for ocular or abdominal complications. Most patients recover fully within weeks to months, though permanent neurological sequelae occur in up to 50% of untreated severe cases. Prevention emphasizes thorough washing of produce, cooking or freezing mollusks and paratenic hosts, and public education in endemic areas to avoid raw consumption of potentially infected items.

Signs and symptoms

Neural manifestations

The primary neural manifestations of angiostrongyliasis due to infection center on involvement, predominantly eosinophilic meningitis resulting from larval migration and inflammatory response in the and brain parenchyma. Severe represents the most common initial symptom, affecting over 90% of cases and typically described as throbbing, diffuse, or migraine-like in intensity, often persisting for 1–7 days. occurs in more than 40% of patients, alongside and , all stemming from meningeal irritation. Paresthesias, manifesting as tingling, numbness, or painful sensations in the , arise from radiculitis or involvement and are noted in approximately 40% of cases, usually resolving within two weeks but occasionally migratory in nature. Less frequent neurological features encompass seizures, altered mental status such as confusion or , and cranial nerve palsies, particularly affecting the sixth or seventh nerves. These symptoms contribute to the progression toward eosinophilic meningitis, where cerebrospinal fluid analysis reveals levels exceeding 10% of total leukocytes, often reaching 20–70%, alongside and elevated protein. In severe, untreated instances—especially among pediatric patients or those who are immunocompromised or otherwise vulnerable—complications may escalate to , with mortality exceeding 90% in cases of eosinophilic meningoencephalitis, or result in permanent neurological deficits such as . Children exhibit heightened severity, with elevated rates of fever (up to 80%), (80%), and convulsions, while adults with conditions like or homelessness have progressed to and required intensive care for altered and .

Ocular involvement

Ocular involvement in angiostrongyliasis represents a rare yet severe complication arising from the direct migration of larvae into ocular structures, potentially occurring independently of or alongside infection. This larval invasion typically targets the anterior chamber (reported in 14 cases), vitreous humor (15 cases), or /subretina (10 cases), inciting intense that manifests as or vitreitis. The condition is often unilateral and can present without preceding in some instances, though may precede ocular signs in others. Patients commonly experience , eye pain, conjunctival hyperemia, , , and floaters as initial symptoms, with loss varying from mild to profound. Fundoscopic evaluation frequently discloses features, including live motile worms within the vitreous, subretinal or intraretinal tracks indicative of larval migration, or macular edema, and occasionally a pale . These findings underscore the mechanical and inflammatory damage inflicted by the parasites during their aberrant migration in human hosts. The incidence of ocular angiostrongyliasis is estimated at approximately 1% among individuals infected with A. cantonensis, though rates of reach up to 16% in broader cohorts of neural cases; involvement appears more frequent in pediatric patients. Untreated progression can culminate in irreversible vision loss, primarily through complications such as , necrotizing retinitis, or secondary . Historical documentation includes surgical interventions for worm extraction, with cases reported as early as 1925 in and subsequent successes in via or anterior chamber procedures, often complemented by corticosteroids to mitigate inflammation.

Abdominal manifestations

Abdominal angiostrongyliasis, caused by Angiostrongylus costaricensis, primarily manifests as acute in the right lower quadrant, often mimicking due to larval migration and inflammation in the intestinal walls. This pain may be accompanied by nonspecific symptoms such as , , or , anorexia, and low-grade fever. Unlike the involvement seen in A. cantonensis infections, A. costaricensis targets the , leading to eosinophilic enteritis characterized by intense eosinophilic infiltration, , and granulomatous inflammation in the and mesenteric arteries. The disease predominantly affects children under 10 years of age, particularly school-aged children, in endemic regions of Central and South America, including , , and other tropical areas with high humidity. Pathological reveals adult worms in the mesenteric and ileocolic arteries, with eggs and larvae sequestered in vascular tissues, often surrounded by thrombi, , and granulomas. Biopsies from affected intestinal segments commonly show eosinophilic arteritis and pseudotumor formation due to these inflammatory responses. Rare complications include intestinal perforation, eosinophilic ascites, gastrointestinal bleeding, and extraintestinal involvement such as hepatic nodules or testicular necrosis from ectopic migration. Diagnosis typically relies on histopathological identification of eggs, larvae, or adults in tissue biopsies, as parasites do not produce detectable eggs in stool.

Incubation and clinical course

The for neural angiostrongyliasis, caused by , typically ranges from 1 to 3 weeks following exposure, though it can extend from as short as 1 day to more than 6 weeks in some cases. In contrast, the for abdominal angiostrongyliasis due to A. costaricensis is less well-defined but is generally thought to span several weeks to months, potentially up to one year. Neural angiostrongyliasis often follows a biphasic clinical course, beginning with an initial systemic phase characterized by nonspecific symptoms such as fever and , which may last hours to days and sometimes include a gastrointestinal . This is followed by an asymptomatic interval of days to weeks, transitioning into a neurological phase that persists for 2 to 8 weeks. The disease is self-limiting in the majority of cases, with most patients achieving resolution within 2 to 8 weeks as the larvae die and are cleared by the host , although chronic sequelae such as neuropathy or persistent paresthesias can endure for months to years in some individuals. For abdominal angiostrongyliasis, the course is typically acute and self-limiting, resolving over weeks with supportive care, though it may lead to prolonged gastrointestinal involvement in severe instances. The severity and progression of angiostrongyliasis are influenced by factors including the larval load, with higher burdens associated with more intense disease, and host immunity, where can exacerbate outcomes. Common progression stages include potential carriage in low-exposure cases, advancement to acute in neural forms, followed by recovery; fatality is rare, with mortality rates below 1% overall, though higher in comatose neural cases.

Etiology

Causative organisms

Angiostrongyliasis is primarily caused by two zoonotic species in the genus Angiostrongylus: A. cantonensis, the rat lungworm, which is responsible for neuroangiostrongyliasis (eosinophilic meningitis), and A. costaricensis, which causes abdominal angiostrongyliasis (intestinal angiostrongyliasis). A. cantonensis is endemic to and the Pacific islands, with its geographic range expanding to include parts of the , the , and . In contrast, A. costaricensis is primarily found in , with reports from countries such as , , and . Both species belong to the family Angiostrongylidae within the superfamily Metastrongyloidea, a group of parasitic nematodes that typically infect the lungs and vascular systems of mammalian hosts. A. cantonensis was first discovered in rats in southern in 1935 by H.T. Chen, marking the initial recognition of this pathogen. A. costaricensis was first identified in humans in during the 1950s, with the species formally described in 1971 by Pedro Morera and Rodolfo Céspedes based on specimens from cotton rats. As zoonotic parasites, Angiostrongylus species have resulted in over 7,000 documented human cases globally as of recent reports, though underdiagnosis likely underestimates the true burden. Humans serve as accidental dead-end hosts, acquiring infection by ingesting larvae from contaminated intermediate hosts like mollusks, but unable to support the parasite's full reproductive life cycle, which requires rodents as definitive hosts.

Morphology and taxonomy

Angiostrongylus species belong to the phylum Nematoda, class , order Strongylida, superfamily Metastrongyloidea, and family Angiostrongylidae. The genus encompasses approximately 19 worldwide, with A. cantonensis and A. costaricensis recognized as closely related, often considered sister taxa based on morphological and molecular analyses. Originally described as Pulmonema cantonensis by Chen in 1935, the nomenclature was revised to , reflecting its classification among metastrongyloid nematodes. Adult worms of Angiostrongylus species are slender, thread-like nematodes with a filiform body that tapers anteriorly. Males measure 10-25 in length and 0.25-0.42 in width, featuring a distinct caudal copulatory supported by bursal rays for . Females are larger, ranging from 17-34 long and 0.28-0.56 wide, with a positioned near the mid-body and a characteristic appearance due to the red intestine and white uterine tubules forming a spiral. Sexual is pronounced, with females being more robust than males. Larval stages exhibit distinct morphologies adapted to . First-stage (L1) larvae are rhabditiform and found in , while third-stage (L3) infective larvae, measuring 425-550 μm in length and 23-34 μm in width, possess a pointed without transverse striations, an anterior knob-like cephalic , a rod-like esophageal portion, and visible excretory pore under light microscopy. The displays fine longitudinal ridges, and the is divided into a and glandular posterior . Species differentiation relies on morphological traits such as bursal ray patterns and spicule in males, supplemented by molecular methods like and sequencing of for precise identification in research settings.

Life cycle

The life cycle of , the primary causative agent of neuroangiostrongyliasis, involves rats as definitive hosts, where adult nematodes reside in the pulmonary arteries and right ventricle. Females deposit eggs in the terminal branches of these arteries, which hatch into first-stage larvae (L1) that migrate to the , are swallowed, and exit the host in . These L1 larvae are then ingested by intermediate hosts, primarily mollusks such as snails ( spp., Biomphalaria spp.) or slugs, where they penetrate the tissues or are ingested and undergo two molts over approximately 2-3 weeks to develop into infective third-stage larvae (L3). Paratenic hosts, including crustaceans (e.g., , ) and amphibians (e.g., frogs), can ingest infected mollusks, allowing L3 larvae to encyst in their tissues without further development until consumed by a definitive host. The cycle completes when a ingests L3 larvae from an infected or paratenic host; the larvae migrate via the bloodstream to the , where they develop into young adults over about 2 weeks before returning to the venous circulation and maturing into adults in the pulmonary arteries within 6-8 weeks, with a prepatent period of 42-45 days. In humans, who serve as accidental dead-end hosts, ingestion of L3 larvae leads to migration to the , where larvae may develop to fourth or fifth stages but cannot mature or reproduce, eventually dying and causing without contributing to . Reservoirs include species such as R. rattus and R. norvegicus. The life cycle of Angiostrongylus costaricensis, responsible for abdominal angiostrongyliasis, follows a similar pattern but with adults residing in the mesenteric arteries of the ileocecal region of rodent definitive hosts, such as the hispid (Sigmodon hispidus). Females produce eggs that enter the intestinal wall capillaries, hatch into L1 larvae, penetrate the lumen, and are shed in feces. These L1 are ingested by intermediate mollusk hosts (e.g., Veronicellidae or Limacidae families), developing into L3 after two molts. Paratenic hosts play a comparable role, harboring encysted L3 without development. Upon ingestion by , L3 migrate to the abdominal lymphatics and then the mesenteric arteries, maturing into adults in approximately 24 days. In humans, ingested L3 reach the mesenteric arteries, where partial maturation and egg production may occur, leading to , but no larvae are shed in stool, preventing cycle continuation.

Transmission

Natural reservoirs and definitive hosts

The primary definitive hosts for , the causative agent of neuroangiostrongyliasis, are rodents of the genus , particularly the (Rattus norvegicus) and the (Rattus rattus), which harbor adult worms in their lungs and pulmonary arteries. These commensal rats maintain the parasite in endemic regions across , the Pacific Islands, and increasingly in the and , where infection prevalence can reach up to 73% in wild rat populations in highly endemic areas like . Other Rattus species, such as R. tanezumi and R. exulans, also serve as competent hosts, with reported infection rates varying from 16.5% in urban Australian settings to up to 77% in some Pacific island rodent communities. For Angiostrongylus costaricensis, responsible for abdominal angiostrongyliasis, the principal definitive host is the hispid cotton rat (Sigmodon hispidus) in the , where adult parasites reside in the mesenteric arteries. This wild species supports endemic transmission cycles in Central and , with infection prevalence as high as 72% documented in surveyed populations from regions like . Additional hosts, including Rattus species and other sigmodontines like Zygodontomys microtinus, contribute to localized persistence, though S. hispidus predominates in natural reservoirs. Wild and commensal rodents collectively sustain persistent transmission cycles for both A. cantonensis and A. costaricensis by shedding infective third-stage larvae in feces, which contaminate environments and infect intermediate hosts such as mollusks. Invasive Rattus populations, often transported via international shipping and trade routes, have facilitated the global spread of A. cantonensis to non-endemic areas, including parts of North America and Europe (e.g., emerging cases in Spain as of 2022), amplifying the risk of establishment in new ecosystems. Ecological factors, such as high-density habitats in and peri-urban areas near settlements, significantly enhance dynamics by increasing opportunities for larval shedding and environmental contamination. In regions like and , commensal populations show variable infection rates that underscore how proximity to activity sustains reservoirs and elevates spillover potential.

Intermediate hosts and vectors

The intermediate hosts of Angiostrongylus cantonensis, the primary causative agent of neuroangiostrongyliasis, are predominantly gastropod mollusks, including both terrestrial snails and slugs as well as some freshwater species. Key examples include the invasive giant African snail (Lissachatina fulica, formerly Achatina fulica) and the golden apple snail (Pomacea canaliculata of the Ampullariidae family), which serve as primary vectors in regions like Southeast Asia and the Pacific. These hosts become infected by ingesting first-stage larvae (L1) from rat feces, allowing the parasite to develop through two molts into infective third-stage larvae (L3) within the mollusk tissues. In A. costaricensis, responsible for abdominal angiostrongyliasis, intermediate hosts are mainly terrestrial slugs from the Veronicellidae family, such as Phyllocaulis variegatus and Sarasinula linguaeformis, prevalent in Central and South America. Within infected mollusks, L3 larvae develop over 2–3 weeks and concentrate primarily in the host's mantle cavity and foot muscles, where they can reach densities of hundreds per individual , facilitating transmission upon ingestion by definitive hosts like rats. This organ enhances larval survival and shedding in slime trails, increasing environmental contamination. Over 20 species worldwide have demonstrated susceptibility, with natural infection rates in endemic populations reaching high levels, such as 86% in certain species like Parmarion martensi in . The global spread of L. fulica has amplified transmission risks, as this has been introduced to more than 50 countries across , , the , and by 2024, often through trade in ornamental plants or as a food source. In addition to true intermediate hosts, paratenic or mechanical vectors play a role by harboring non-developing L3 larvae, including freshwater prawns, land crabs, frogs, and even contaminated with mollusk slime containing shed larvae. These vectors extend the parasite's reach without completing its developmental cycle, particularly in human-populated areas where contaminated produce is common.

Human exposure routes

Humans acquire angiostrongyliasis primarily through the accidental ingestion of third-stage (L3) larvae of , the causative agent, which are found in infected intermediate hosts such as snails and slugs or paratenic hosts like freshwater prawns and . The most direct route involves the deliberate consumption of raw or undercooked snails or slugs, which serve as intermediate hosts containing viable L3 larvae; for instance, the giant African snail (Achatina fulica) is a common vector in endemic areas. Similarly, eating raw or undercooked prawns or other crustaceans acting as paratenic hosts can transmit the larvae, as these organisms harbor the infective stage without further development. Another significant exposure pathway is the ingestion of contaminated vegetables or produce, such as , where L3 larvae may adhere via snail or slug mucus trails or be present in small paratenic hosts inadvertently consumed. This route often occurs unintentionally during food preparation or eating raw greens, highlighting the risk in regions with high gastropod populations on agricultural lands. Cultural practices in certain regions, particularly in Pacific islands and , contribute to higher exposure risks through the consumption of raw mollusks in traditional dishes, such as salads or "," where undercooked snails are incorporated as delicacies. These habits, rooted in local cuisines, have been linked to clusters of cases in endemic communities. Accidental exposures are common, especially among children who may handle or ingest slugs during play, or individuals with poor hand hygiene after gardening or outdoor activities in infested areas. Such non-food-related ingestions underscore the parasite's environmental prevalence and the need for awareness in vulnerable populations. A notable outbreak illustrating the contamination route occurred in in 2000-2002, where 12 tourists developed eosinophilic meningitis after consuming a tainted with A. cantonensis larvae at a . This incident, traced to contaminated produce, affected all 12 individuals who ate the salad, demonstrating how shared meals can amplify transmission in non-endemic travelers. Infection can result from ingesting even small numbers of L3 larvae, and higher may correlate with increased severity due to greater larval and tissue burden. This low threshold emphasizes the potency of accidental exposures in endemic settings.

Pathophysiology

Larval migration and organ tropism

Upon ingestion of third-stage larvae (L3) of Angiostrongylus species in contaminated food or water, the larvae penetrate the intestinal mucosa in the and enter the bloodstream via the mesenteric veins. From there, they are carried through the portal circulation to the liver and then into the systemic venous system, eventually reaching the arterial circulation. In infections with A. cantonensis, the larvae exhibit strong neurotropism, migrating via the carotid arteries to the (CNS), where they penetrate the and to mature in the subarachnoid space. These larvae reach the CNS within 24 hours post-ingestion and undergo molting to the fourth stage around 7 days and fifth stage by approximately 12 days, though full maturation to adults does not occur in humans. In contrast, A. costaricensis larvae show for vascular tissues, migrating to the mesenteric arteries and branches near the ileocecal region, where they develop into adults and localize in the intestinal , leading to vascular occlusion by eggs and larvae. Larvae generally arrive at their target organs within 24 hours for A. cantonensis, with up to 24 days for A. costaricensis development to adulthood, with peak inflammatory responses occurring 2–4 weeks post-infection as larvae begin to die. is facilitated by the larvae's enzymatic to aid penetration and in the bloodstream, though specific chemotactic cues toward neural or vascular remain under investigation. As larvae die in ectopic sites, they elicit recruitment of to the affected tissues, resulting in granuloma formation around the parasites, which contributes to localized damage in the CNS for A. cantonensis or intestinal vessels for A. costaricensis. This process amplifies tissue injury through host immune responses but is limited in humans as a dead-end .

Immune response and tissue damage

The to Angiostrongylus is predominantly Th2-mediated, characterized by a robust of type 2 immunity that drives recruitment and . In humans and experimental models, this response manifests as marked peripheral blood , often reaching up to 50% of total leukocytes, alongside and () . Key cytokines such as interleukin-5 (IL-5) and IL-13 play central roles, with IL-5 promoting differentiation, survival, and migration to sites, while IL-13 enhances production and alternative , further amplifying the inflammatory milieu. This Th2 skewing is evident in both (causing neuroangiostrongyliasis) and A. costaricensis (causing abdominal angiostrongyliasis), where it correlates with severity. Tissue damage in angiostrongyliasis arises from a combination of direct mechanical inflicted by migrating larvae and indirect mediated by activated . Larval penetration and movement through tissues cause initial disruption, but the ensuing eosinophil releases toxic cationic proteins, including major basic protein (MBP), which induce and exacerbate local . These proteins damage host cell membranes and contribute to formation around dying parasites, leading to chronic inflammatory foci. In non-permissive hosts like humans, where larvae do not complete their life cycle, this immune-mediated damage predominates over effective parasite clearance. In the (CNS), the Th2 response following larval migration leads to (BBB) breakdown, allowing infiltration into the and . This triggers , with -derived mediators causing endothelial damage and vascular leakage, which can culminate in due to obstructive and increased . reactions, driven by Th2 cytokines and IgE production, further contribute to neurological symptoms such as paresthesias, reflecting nerve irritation from localized and activity. Abdominal angiostrongyliasis elicits a similar response in the , where intense infiltration targets arterial walls harboring larvae and eggs. Granulomatous develops around affected vessels, promoting and subsequent ischemia in the gut wall, which can lead to , ulceration, or . levels in blood and tissues may exceed 80% in severe cases, intensifying these vascular complications.

Differences between species

Angiostrongylus cantonensis exhibits pronounced neurotropism in aberrant hosts like humans, where third-stage larvae migrate to the (CNS), particularly the and subarachnoid space, leading to eosinophilic characterized by intense from larval death without further maturation. In contrast, A. costaricensis demonstrates vascular tropism targeted to the , with larvae migrating to the mesenteric arteries and ileocecal region, where they can partially develop into adults, produce eggs and first-stage larvae, and induce chronic eosinophilic enteritis through granulomatous reactions in intestinal tissues. The neural form of angiostrongyliasis caused by A. cantonensis tends to be more acute and symptomatic, manifesting with severe headaches, , paresthesias, and potential neurological deficits due to CNS invasion and larval demise, though most cases resolve with supportive care. Conversely, the abdominal form from A. costaricensis is often milder initially but carries risks of complications such as intestinal obstruction, , or from egg deposition and larval sequestration, sometimes necessitating surgical intervention. Geographically, A. cantonensis is adapted for pulmonary arterial residence in definitive rat hosts, facilitating a life cycle that includes lung migration, which contributes to its neurotropic deviation in humans across tropical and subtropical regions. A. costaricensis, however, is specialized for mesenteric vascular habitation in rodent hosts, aligning with its abdominal in humans and endemicity in the . Both species induce peripheral eosinophilia in infected individuals, providing diagnostic overlap, yet their pathologies diverge markedly by site: CNS-focused for A. cantonensis versus gut-specific granulomas for A. costaricensis. Genomic analyses as of 2024 reveal shared ancestry within the Angiostrongylus but highlight divergent adaptations, with A. cantonensis showing high and cryptic lineages potentially influencing pathogenicity, while A. costaricensis exhibits distinct mitochondrial variations supporting its regional specialization in mammalian mesenteric systems.

Diagnosis

Clinical assessment

Clinical assessment of suspected angiostrongyliasis begins with a detailed exposure history, focusing on recent travel or residence in endemic regions such as or the Pacific Islands, and consumption of raw or undercooked snails, slugs, freshwater prawns, crabs, or contaminated vegetables. The typically ranges from 1 to 6 weeks, aligning with the timeline of potential exposure, which helps correlate symptoms like severe and to the infection. In abdominal cases caused by Angiostrongylus costaricensis, history may include ingestion of raw mollusks in Central and South America. Physical examination emphasizes neurological evaluation for signs of meningeal irritation, including , positive Kernig's and Brudzinski's signs, , paresthesias, and cranial nerve deficits such as abducens . In neuroangiostrongyliasis due to A. cantonensis, and radiculitis may be evident, while abdominal forms present with right lower quadrant tenderness and a palpable mass mimicking . Initial laboratory screening often reveals peripheral exceeding 500/μL in 50-70% of neuroangiostrongyliasis cases, providing supportive evidence prior to confirmatory testing. Differential diagnosis includes bacterial or viral (e.g., enteroviral), , , and non-infectious causes like ; abdominal presentations may suggest or . Severity employs criteria such as duration exceeding 1-2 weeks and elevated peripheral counts to prioritize urgent and potential initiation. In children, particularly those under 5 years, should note , , and higher risk of severe neurological outcomes due to increased likelihood of accidental of hosts. This initial guides progression to laboratory confirmation for definitive management.

Laboratory confirmation

Laboratory confirmation of angiostrongyliasis primarily involves analysis of (CSF) obtained via , which reveals characteristic findings supporting the when clinical suspicion exists. CSF typically shows pleocytosis with more than 10% , elevated protein levels, and normal glucose concentrations, distinguishing it from bacterial . Serological tests, such as or , detect anti- antibodies in serum or CSF, offering sensitivities of 80-95% depending on the antigen used, such as the 31 kDa band in immunoblots. These assays are particularly useful in the subacute phase but may require confirmation due to potential with other helminths like Gnathostoma spinigerum. Polymerase chain reaction (PCR) amplification of DNA from CSF or ocular fluid is a highly specific confirmatory method, with real-time assays detecting A. cantonensis DNA even in low-burden infections. The U.S. Centers for Disease Control and Prevention (CDC) provides this test for CSF specimens, which outperforms in early infection stages. As of July 2025, a more sensitive real-time assay is available through the Hawaii State Laboratories Division, enabling detection in CSF without a minimum threshold for earlier diagnosis. Stool examination is not useful for diagnosis in either form, as parasites do not produce eggs or shed larvae into in human infections. Peripheral blood counts, often elevated, can be serially monitored to track progression and response to , typically peaking at 2-4 weeks post-infection before declining. Diagnostic limitations include in serological tests with other antigens, necessitating species-specific assays like for definitive identification, and the potential for false negatives in early or resolved infections.

Imaging and ancillary tests

In neuroangiostrongyliasis caused by Angiostrongylus cantonensis, (MRI) of the is a key ancillary test for evaluating involvement and complications such as or . MRI commonly reveals leptomeningeal thickening and enhancement, particularly in the basal cisterns and sulci, indicative of eosinophilic meningitis. Parenchymal hyperintensities appear as high-signal lesions on T2-weighted and (FLAIR) sequences in the , , , or , reflecting inflammatory edema from larval migration. Linear or curvilinear hyperintense tracks on T2/FLAIR images, often in the or subarachnoid space, suggest paths of larval movement, while post-contrast enhancement shows nodular or stick-shaped lesions measuring 3-14 mm, peaking at 5-8 weeks post-infection. These findings correlate with cerebrospinal eosinophilia and aid in monitoring treatment response, with resolution typically occurring over 4-22 weeks. Computed tomography (CT) scans serve as an initial imaging modality in suspected cases, particularly to detect or rule out other causes of neurological symptoms. In neuroangiostrongyliasis, non-contrast head often shows no focal parenchymal lesions but may reveal ventricular enlargement due to communicating from meningeal . For abdominal angiostrongyliasis due to A. costaricensis, abdominal is useful for identifying complications like bowel wall thickening or masses mimicking or tumors. Contrast-enhanced demonstrates edematous ileocecal wall thickening, segmental involvement, moderate , or granulomatous pseudotumors in the intestine, helping differentiate from . Ultrasound plays a supportive role in abdominal cases, detecting bowel wall thickening or mesenteric that suggests eosinophilic . In severe presentations, it may reveal ileal or cecal wall up to 10 mm thick, hyperemia, or reactive lymph nodes greater than 1 cm, guiding surgical decisions. For ocular angiostrongyliasis, ocular or B-scan can visualize intraocular larvae as motile, hyperechoic structures in the vitreous or subretinal space, while fundoscopy identifies subretinal tracks, retinal , hemorrhages, or pale optic discs indicative of . Electroencephalography (EEG) is employed in neuroangiostrongyliasis patients with seizures to assess cortical involvement. It typically shows diffuse slowing with theta or delta waves, reflecting from larval-induced , though epileptiform discharges are uncommon. is rarely performed but confirmatory in abdominal angiostrongyliasis when imaging is inconclusive. of intestinal or appendiceal tissue reveals eosinophilic arteritis with larval forms in arterial walls, accompanied by granulomatous and .

Prevention

Individual precautions

Individuals in endemic areas or travelers to regions such as the Pacific islands and should avoid consuming raw or undercooked snails, slugs, freshwater prawns, or other potential intermediate hosts like land crabs and frogs, as these can harbor infective larvae of leading to neuroangiostrongyliasis. To ensure safety, such foods must be cooked thoroughly to an internal temperature of at least 74°C (165°F), which inactivates the larvae. Fresh produce, particularly in areas where snails and slugs are common, poses a risk of contamination through slime trails containing larvae, often via contaminated salads or unwashed greens. Thorough washing of fruits and vegetables with , followed by rinsing each leaf individually and peeling when possible, helps remove potential contaminants including and larvae. The Centers for Disease Control and Prevention (CDC) recommends thorough washing of all raw produce before consumption in high-risk areas. Children are particularly vulnerable due to their tendency to handle or ingest mollusks, so parents should educate them on the dangers of touching or putting snails, slugs, or contaminated in their mouths. In endemic regions, supervising children's outdoor play and discouraging contact with these hosts is essential. When or handling soil in areas with invasive snails, wearing gloves prevents direct skin contact with potentially infected mollusks, followed by thorough handwashing with and water. General practices, including handwashing after any outdoor activities or contact with potentially contaminated surfaces, further reduce accidental ingestion risks. For pet owners, managing the home environment involves controlling rat populations and removing invasive snails or slugs from yards and gardens to limit the parasite's life cycle, as rats serve as definitive hosts and pets like dogs can act as accidental hosts by consuming infected mollusks. Preventing pets from eating snails or slugs through supervision and deworming where applicable helps mitigate secondary exposure risks.

Environmental and public health measures

Control of intermediate hosts, primarily snails and slugs, forms a cornerstone of environmental measures against Angiostrongyliasis. Manual removal involves hand-picking mollusks at night or after rain using gloves or tools to minimize contact, followed by disposal in soapy water or 15% saltwater solutions; this method is particularly effective for larger like the giant African snail (Lissachatina fulica). Chemical interventions employ molluscicides such as metaldehyde-based baits (e.g., Deadline®), which achieve 90-100% mortality in vectors like the semi-slug Parmarion martensi within 7-14 days, though they pose risks to non-target . Biological controls, including the introduction of predatory ducks in endemic agricultural areas, target populations such as Pomacea canaliculata, reducing infestation levels in rice paddies and farms. Management of rat populations, the definitive hosts for , relies on integrated strategies in urban and rural settings. and rodenticides are deployed to lower reservoir densities of species like Rattus rattus and R. norvegicus, thereby interrupting the parasite's , although complete eradication remains impractical due to rats' widespread adaptability. programs are essential for early detection and containment of invasive vectors. Monitoring of L. fulica occurs at international ports and in high-risk regions, with the enforcing quarantines and eradication protocols in areas like to curb establishment; ongoing and eradication efforts continue, with quarantines enforced in several counties (e.g., Pasco, Lee, Broward) as of 2024 to prevent establishment. Advanced diagnostic techniques, such as microscopic examination of snail buccal cavities, enable rapid identification of Angiostrongylus larvae in intermediate hosts like , supporting epidemiological tracking in endemic zones including parts of and the Pacific. Public education campaigns promote community-wide adherence to protocols in high-risk countries, drawing on guidelines that stress avoiding raw or undercooked mollusks and thorough washing of produce to prevent accidental ingestion of larvae. In regions like , statewide media initiatives, partnered with broadcasters, have disseminated information on transmission risks since 2017, significantly raising awareness and reducing reported cases through targeted messaging on . Agricultural practices mitigate contamination by incorporating physical barriers and regulatory measures. Electrified metal tape systems, powered by low-voltage batteries and installed around crop perimeters, have demonstrated up to 90% efficacy in preventing slug entry into fields, as tested with vectors like Parmarion martensi and Deroceras reticulatum in Hawaii. Strict import restrictions on live mollusks by authorities like the USDA further limit the introduction of invasive species capable of harboring the parasite. Addressing climate-driven expansion requires adaptive strategies, as rising temperatures facilitate the parasite's northward migration beyond tropical zones. Ecological modeling indicates increased habitat suitability in temperate regions, with autochthonous already reported in rats from , , in 2021, signaling potential establishment across . As of 2025, surveillance indicates continued circulation in urban rats in and potential spread to other areas, underscoring the need for enhanced monitoring in warming climates.

Treatment

Antiparasitic drugs

Treatment of angiostrongyliasis is primarily supportive, as there is no proven specific therapy. Anthelmintics such as are sometimes used adjunctively for neuroangiostrongyliasis caused by , particularly with corticosteroids to target larval stages, though their efficacy is debated and they carry a risk of exacerbating from dying parasites. When used, the suggested dosage is 15 mg/kg/day, administered in two divided doses for 2 weeks, ideally initiated concurrently with or after corticosteroids within 2 weeks of exposure. Mebendazole and ivermectin are considered alternative anthelmintics with limited evidence, particularly for the abdominal form caused by A. costaricensis, where anthelmintics are not recommended due to potential worsening of symptoms and lack of controlled data. has lower penetration than , and does not adequately cross the blood-brain barrier for CNS-migrated larvae. For abdominal cases, no drugs have demonstrated clear benefit in humans. Animal studies show can reduce larval burden, with up to 80% worm reduction in models when combined with other agents. Some human reports and a of case series indicate symptom improvement with albendazole-corticosteroid combinations in up to 97.87% of 323 patients, such as shorter duration, though randomized trials show no added benefit over corticosteroids alone, and the infection is often self-limiting. Major guidelines caution against routine use due to unproven efficacy and risks. Contraindications for include use without concurrent therapy in severe CNS cases due to risk; it is also cautioned in (FDA Category C) based on animal studies showing potential teratogenicity. Rare adverse effects like or elevated liver enzymes require monitoring. As of 2023 reviews, albendazole remains a debated option in combination regimens, such as with pyrantel pamoate for potential post-exposure use in animal models, but ongoing trials in endemic areas like Thailand have not yet provided definitive results supporting routine application.

Anti-inflammatory and symptomatic therapies

The primary anti-inflammatory therapy for neuroangiostrongyliasis, the most common form of angiostrongyliasis caused by Angiostrongylus cantonensis, involves corticosteroids to mitigate central nervous system edema and the eosinophilic inflammatory response during the acute phase. Prednisone or prednisolone is typically administered at 1 mg/kg/day (up to 60 mg/day for adults) in divided doses for 2 weeks, followed by a gradual taper over 2 weeks to prevent rebound inflammation. This regimen has been shown in a randomized, double-blind, placebo-controlled trial to significantly reduce headache duration (median 5 days versus 13 days) and the need for repeated lumbar punctures, with only 9.1% of treated patients experiencing persistent headache at 2 weeks compared to 45.5% in the placebo group. Symptomatic relief focuses on managing common manifestations such as severe , , and . Analgesics like acetaminophen are recommended as first-line for mild to moderate , while opioids (e.g., or ) may be used judiciously for severe cases due to risks of and dependence; nonsteroidal drugs (NSAIDs) should be avoided when corticosteroids are co-administered because of increased risk. Antiemetics such as are employed for and in the early stages to improve patient comfort. Therapeutic lumbar punctures (removing 20–40 mL of ) provide additional relief from elevated and associated symptoms. In the rarer abdominal form caused by A. costaricensis, which primarily affects the intestines and presents with milder symptoms, anti-inflammatory therapies are generally not required unless severe leads to significant , in which case corticosteroids may be considered supportively. Overall, these measures aim to alleviate acute symptoms while the infection resolves naturally, with monitoring for complications such as worsening neurological deficits.

Management of complications

In severe cases of neural angiostrongyliasis caused by , may develop due to inflammatory obstruction of pathways, occasionally necessitating neurosurgical intervention such as to relieve . This procedure is rare, typically reserved for patients with rapidly progressive symptoms unresponsive to repeated lumbar punctures or medical management, as conservative approaches often suffice for resolution. Ocular angiostrongyliasis, occurring in approximately 1% of infections, can lead to intraocular larval migration causing vision-threatening inflammation or damage, where pars plana vitrectomy is employed to extract live worms from the vitreous cavity and preserve visual function in select cases. Surgical intervention, often preceded by laser photocoagulation to immobilize the parasite, has been performed successfully without postoperative complications like in reported series. For abdominal angiostrongyliasis due to A. costaricensis, complications such as intestinal , obstruction, or from granulomatous may require urgent , including resection of affected bowel segments to prevent or . Histopathological examination of surgical specimens confirms the by identifying larvae, eggs, or worms in the intestinal wall. Post-recovery rehabilitation is essential for patients with residual neurological sequelae, such as , , or , involving multidisciplinary physical and to improve , strength, and daily function. Long-term exercise programs and strategies address persistent symptoms that can impair quality of life for months or years. Ongoing monitoring for chronic deficits, which affect approximately 5-10% of severe cases, includes serial (e.g., MRI) to track meningeal enhancement or , alongside neurocognitive assessments to evaluate , , and motor skills. Regular follow-up helps detect delayed complications like focal deficits or , guiding adjustments in rehabilitative care. Hospitalized patients benefit from comprehensive supportive care, including nutritional supplementation to counter from gastrointestinal symptoms or reduced intake, and prophylactic antibiotics to prevent secondary bacterial infections amid eosinophilic . Intravenous hydration and monitoring further stabilize critically ill individuals. Early intervention in complications improves overall prognosis by mitigating permanent damage.

Epidemiology

Global distribution and prevalence

Angiostrongylus cantonensis, the primary causative agent of neuroangiostrongyliasis, is endemic in more than 30 countries, predominantly in tropical and subtropical regions of , , and the Pacific Islands. The highest incidence occurs in the region, with reporting hundreds of cases annually, particularly in the northeast where rates can reach up to 23 per 100,000 population. The parasite has spread to the and , with established foci in countries such as , , , , and by 2024, often facilitated by the global trade of infected rats and invasive snails. In contrast, Angiostrongylus costaricensis, responsible for abdominal angiostrongyliasis, is geographically restricted to Central and South America, with reports from at least 24 sites including , , , , and . Prevalence in endemic areas like southern shows seropositivity rates of 29.8% to 66% in humans, while has documented hundreds of cases over recent decades through serological testing. The disease remains underreported across these regions due to nonspecific symptoms mimicking other abdominal conditions. Globally, over 7,000 human cases of angiostrongyliasis have been confirmed since the first report in 1945, though this figure is likely an underestimate due to frequent misdiagnosis as bacterial or other disorders, limited access to confirmatory diagnostics like or in rural tropical areas, and underreporting in low-resource settings. Emerging foci include , a recognized hotspot in the United States with ongoing transmission; , where 28 cases were documented from 1971 to 2018 amid rising trends; and , where reported human cases are primarily imported, though local detections in rats and gastropods have occurred in and as of 2025. In endemic hotspots, infection prevalence in definitive hosts and intermediate hosts ranges from 10% to 50%, underscoring the parasite's efficient zoonotic cycle.

Risk factors and emerging trends

High-risk groups for angiostrongyliasis primarily include children, particularly those exhibiting behavior, which increases accidental ingestion of infected s or contaminated produce. Immunocompromised individuals and adults with vulnerabilities face heightened risks due to reduced ability to avoid or recognize exposure sources. In endemic zones, consumers of raw or undercooked snails, slugs, freshwater prawns, or contaminated with mollusk slime are especially susceptible, as these practices directly facilitate larval ingestion. Environmental factors significantly contribute to the disease's transmission, with invasive snail species such as the giant African snail (Lissachatina fulica) serving as efficient intermediate hosts that amplify parasite spread in new regions. Climate change exacerbates this by altering temperature and precipitation patterns, enabling the parasite's range expansion into previously temperate areas unsuitable for its life cycle. Projections indicate increased habitat suitability in regions with rising temperatures and rainfall, potentially broadening transmission dynamics by the mid-21st century. Recent outbreaks underscore these risks, including detection of A. cantonensis in rats in , , USA, from 2019 to 2022, indicating local transmission potential. In , three pediatric cases of locally acquired A. cantonensis were confirmed between 2021 and 2022, highlighting vulnerabilities in children through inadvertent contact with infected or produce. Urbanization and global trade further accelerate zoonotic spillover by facilitating the movement of infected rats and snails via shipping and . Reviews from 2024 note a rising incidence in non-endemic areas, such as parts of and the continental , driven by these factors. In , socioeconomic conditions like and inadequate heighten exposure to the abdominal form of angiostrongyliasis caused by A. costaricensis, as impoverished communities often rely on unmanaged natural environments where intermediate hosts thrive. Poor limits access to clean water and proper waste disposal, indirectly promoting proliferation and human-mollusk interactions. Surveillance efforts have improved post-2020, with enhanced reporting through international networks revealing previously undetected foci, such as detections in invasive mollusks across the , Mediterranean , and new records in . This increased vigilance, supported by organizations like the CDC, has documented northward range expansions and urban transmissions, aiding in targeted responses.

History

Discovery and early cases

The nematode Angiostrongylus cantonensis, the primary causative agent of neuroangiostrongyliasis, was first discovered in 1935 in the pulmonary arteries of rats collected in Guangzhou (formerly Canton), China, by parasitologist Hsin-Tao Chen. Initially classified as Pulmonema cantonensis, it was later reclassified into the genus Angiostrongylus due to morphological similarities with other metastrongylid nematodes. This finding established the parasite's zoonotic potential in rodent hosts, though its role in human disease remained unrecognized for over a decade. The first documented human infection with A. cantonensis occurred in 1944 in , reported in 1945 by Nomura and Lin as the cause of eosinophilic meningitis in a 15-year-old boy who died from severe neurological symptoms. The case involved larval migration to the , leading to and eosinophil accumulation in the (CSF), but the parasite's identity was not fully confirmed at the time due to limited diagnostic tools. This marked the initial link between the rat lungworm and human illness, though sporadic cases in went largely unexplained until the 1960s. In the Americas, Angiostrongylus costaricensis, responsible for abdominal angiostrongyliasis, emerged as a distinct species. The first human case was reported in 1952 in a seven-year-old child in , presenting with , , and appendicitis-like symptoms, though the parasite was not formally identified until later. The species was described in 1971 from specimens in the mesenteric arteries of wild rodents (cotton rats) in by Pedro Morera and Rodolfo Céspedes, with additional human abdominal cases documented throughout the , often involving intestinal granulomas and eosinophilic infiltration. Early nomenclature for A. cantonensis infections commonly referred to the condition as "rat lungworm disease," reflecting its primary habitat in rodent pulmonary vasculature. Diagnostic advances in the included the recovery and morphological identification of A. cantonensis larvae from CSF and , facilitated by improved techniques that confirmed the parasite's role in eosinophilic meningitis. A pivotal 1961 epidemiological investigation by Rosen, Laigret, and Bories in the Pacific Basin, including and , linked outbreaks to consumption and gained international attention through reports highlighting the parasite's spread, solidifying its global recognition as a concern.

Notable outbreaks and research milestones

The first recognition of human angiostrongyliasis occurred in 1944 when a 15-year-old boy in developed eosinophilic meningitis after consuming raw snails, with the causative agent identified in a 1945 report by Nomura and Lin, though not fully confirmed at the time. Subsequent cases in during the and were similarly unexplained, highlighting the disease's endemicity in without a confirmed . A pivotal milestone came in when Angiostrongylus cantonensis larvae were recovered from the and brain tissue of a patient in , definitively linking the rat to eosinophilic meningoencephalitis; this discovery, reported in subsequent publications, established the parasite's role in human disease and spurred . Building on this, experimental infections in animals during the early 1960s elucidated the parasite's , confirming rats as definitive hosts and snails as intermediate hosts, which informed prevention strategies. Notable outbreaks emerged in the late , including a 1982 incident in where 16 Korean fishermen developed severe eosinophilic radiculomyeloencephalitis after ingesting raw giant African snails (Achatina fulica), marking the first documented cluster of life-threatening neuroangiostrongyliasis and prompting studies on paratenic hosts. In 1998–1999, experienced significant outbreaks in with 17 confirmed cases among Thai laborers who consumed raw golden apple snails (Pomacea canaliculata), underscoring the risks of invasive snail species and leading to enhanced regulations. The early saw the disease spread beyond traditional endemic areas, with a 2004 outbreak in affecting 12 U.S. travelers who ate contaminated salad, representing one of the largest imported clusters to and highlighting tourism-related transmission risks. In , cases surged from 2005 onward, culminating in 82 reported infections between 2007 and 2017, primarily linked to undercooked snails and slugs, which drove research into local gastropod reservoirs and improved diagnostic assays. China reported multiple large-scale outbreaks starting in 1997, with a major epidemic in from October 2007 to March 2008 affecting 181 suspected cases (33 confirmed) due to consumption of raw Ampullarium canaliculatus snails, representing the largest documented cluster and catalyzing nationwide programs. This period also advanced serological diagnostics, with enzyme-linked immunosorbent assays () developed in the late 2000s enabling rapid detection and seroprevalence studies. Recent milestones include the 2018 detection of A. cantonensis in , (reported in 2022), marking its first confirmed establishment in and prompting genomic studies on invasion pathways via invasive rats and snails. In 2025, the parasite was detected for the first time in and , , indicating further expansion into new regions, alongside identification of new endemic foci in the . Ongoing research emphasizes climate-driven expansion, with over 2,800 global cases documented by 2008, and continued increases due to and . As of November 2025, cases persist in , with efforts focusing on surveillance and education.