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Angiostrongyliasis is caused by the parasitic nematode Angiostrongylus cantonensis, commonly known as the "rat lungworm." This infectious agent is the most common cause of eosinophilic meningitis in humans; eosinophilic meningitis secondary to infection with A cantonensis is referred to as neuroangiostrongyliasis. Rats are the definitive hosts and the primary transmitters, while snails and slugs act as intermediate hosts. Humans become accidental hosts by consuming contaminated food. Once ingested, the larvae travel from the intestines to the brain, where upon death, the larvae elicit a strong immune response, leading to meningitis and severe neurological symptoms, including headaches, cranial nerve palsies, and, in severe cases, coma or death. Diagnosis is based on clinical history, laboratory findings, and cerebrospinal fluid eosinophilia. While the infection is most prevalent in the Asia-Pacific region, cases have been reported globally. Treatment of A cantonensis infection focuses on managing symptoms, reducing inflammation, and lowering intracranial pressure; most cases resolve spontaneously with supportive care. This activity for healthcare professionals enhances the learner's competence in recognizing the clinical features of eosinophilic meningitis, performing the recommended evaluation, and implementing an appropriate interprofessional management approach to improve patient outcomes. Objectives: Differentiate neuroangiostrongyliasis from other causes of meningitis, especially in patients presenting with eosinophilia in cerebrospinal fluid. Screen patients with relevant travel history or exposure to potential vectors, such as snails or contaminated food, for Angiostrongylus cantonensis infection. Implement appropriate diagnostic workups, including cerebrospinal fluid analysis for eosinophilia and serological testing, for patients with Angiostrongylus cantonensis infection. Apply interprofessional team strategies to improve care coordination and outcomes in patients with angiostrongyliasis. Access free multiple choice questions on this topic.

Angiostrongylus cantonensis, commonly known as the "rat lungworm," is a parasitic nematode that causes eosinophilic meningitis in humans. Rats are the definitive hosts and the primary transmitters, while snails and slugs act as intermediate hosts.[1] When ingested inadvertently by human hosts, these nematodes can travel to the brain, eliciting hypersensitive immune reactions upon their death. These immune reactions can result in eosinophilic meningitis and ongoing sequelae, including focal neurological deficits, coma, and death.[2] The parasite is most prevalent in Asia-Pacific; however, outbreaks and sporadic cases have been reported outside endemic areas. Moreover, 9 species have been identified, but A cantonensis and Angiostrongylus costaricensis remain the most important human pathogens.[3] Diagnosis is based on clinical history, laboratory findings, and cerebrospinal fluid eosinophilia. Treatment of A cantonensis infection focuses on managing symptoms, reducing inflammation, and lowering intracranial pressure. Most cases resolve spontaneously with conservative interventions, including corticosteroids and antihelminthic medications. In some cases, laser and surgical treatment may be used.

Angiostrongylus infection in humans is incidental and occurs because of the consumption of infected intermediate or paratenic hosts, including snails or their excrement. Ingested larvae travel from the intestinal mucosa into the bloodstream, where they mature, and adult female nematodes lay eggs in the terminal branches of the pulmonary arteries. The eggs hatch, and the larvae move into the pharynx. They are coughed and subsequently swallowed and travel to the intestinal mucosa, where they are expelled through feces. The nematode is passed between rodents and slugs or snails in its natural transmission lifecycle. Rats are definitive hosts for the nematode. The adult nematode enters the rat's bloodstream, where it matures. Fertilization then occurs, followed by the production of eggs, which are released into the blood; the eggs are lodged in the smaller pulmonary vessels and hatch.[4] The first-stage nematodes break into the airways and then migrate to the upper airways and pharynx, where they are swallowed, passed down the gastrointestinal tract, and lodged into the feces. Snails and slugs (intermediate hosts) ingest these larvae, which mature into the third-stage larvae (infective form) that are passed on to the definitive hosts again when the definitive hosts consume infected intermediate hosts. Third-stage larvae are neurotropic and develop into young adults in the brains of definitive hosts. They then migrate to the venous system and finally reach the pulmonary vasculature, where they sexually mature, and the female worms lay eggs.[5] Some other transports (paratenic) hosts, including snails, frogs, centipedes, reptiles, and crustaceans (eg, prawns, crabs, and freshwater shrimp), pick up the third-stage larvae by ingesting the infected intermediate hosts, which are then passed on to the definitive host that ingest these paratenic hosts.[6] Paratenic hosts do not allow the nematode to reproduce but can be further consumed by definitive hosts. Vegetables covered with snail slime can also be a source of infection.[3][4]

Third-stage larvae are neurotropic and develop into young adults in the brains of definitive hosts. They then migrate to the venous system and finally reach the pulmonary vasculature, where they sexually mature, and the female worms lay eggs.[5] Some other transports (paratenic) hosts, including snails, frogs, centipedes, reptiles, and crustaceans (eg, prawns, crabs, and freshwater shrimp), pick up the third-stage larvae by ingesting the infected intermediate hosts, which are then passed on to the definitive host that ingest these paratenic hosts.[6] Paratenic hosts do not allow the nematode to reproduce but can be further consumed by definitive hosts. Vegetables covered with snail slime can also be a source of infection.[3][4] The nematode inside the central nervous system, especially in the subarachnoid space, elicits intense eosinophilic inflammation due to the host immune response that causes acute eosinophilic meningitis. With severe infestations in human hosts, other inflammatory manifestations can result, including radiculitis, cranial neuropathy, myelitis, encephalopathy, coma, and even death. The nematode eventually dies in the nervous system; therefore, humans do not transmit A cantonensis.[7]

Angiostrongylus spp are classically endemic to the Asia-Pacific regions, with the highest incidence in Thailand and Malaysia. Additional areas of inhabitance include the Pacific basin, China, Vietnam, the Philippines, Taiwan, and Hawaii.[8][9] Dissemination of infected rats has spread the parasite to nonendemic areas, including Africa, South America, Australia, the Caribbean islands, and Louisiana. Travel-related exposures have been attributed to sporadic cases detected in Europe and the United States.[10] The incubation period usually ranges from 1 to 3 weeks but can last as long as 6 weeks.[9] The global incidence of angiostrongyliasis is difficult to discern due to its intermittent transmission but has been estimated to be as high as 2 per 100,000 individuals in Thailand.[11] In these organisms, the parasite is not reproduced, but transmission to humans is possible by the consumption of the affected organisms.

Clinical pathology in humans is generally based on the location of the immune response to A cantonensis. For instance, these nematodes in the central nervous system (CNS) produce an intense localized inflammatory response with an eosinophilic reaction, resulting in the classic presentation of eosinophilic meningitis. The eye may also occasionally be the site of infection.[12][13][14] High expression of interleukin 33 with a TH2 response has been seen in mouse models of A cantonensis infection, associated with an inflammatory response in eosinophilic meningitis.[15] When the inflammation is more severe or affects other areas of the CNS, cranial nerve deficits, ataxia, radiculitis, encephalitis, coma, and death may result.[2] This inflammatory response is particularly prominent in those with immunosuppression. However, restoration of humoral responses can reduce damage to the CNS.[16]

The pathological features in humans have been uncommonly described but are consistent. Lymphocytes, plasma cells, and eosinophils are predominant in the brain, infiltrating into meninges and surrounding vessels that perforate into brain and spinal cord tissue. Microcavities due to larval migration may be seen on light microscopy, ranging in size from 0.1 mm to 2 mm.[17] Occasional areas of hemorrhage and cellular reactions may accompany parenchymal injury and debris, including dead and living larvae. In lung tissue, larvae may be found in pulmonary vessels.

The clinical syndrome seen with A cantonensis infection is due to the intense inflammatory reaction of the dying parasites. The most common cause of eosinophilic meningitis remains angiostrongyliasis. Headache is the most common symptom in up to 95% of patients, followed by neck stiffness, nausea (28%), and vomiting (38%).[18][19] Paresthesia and hyperesthesia lasting several weeks can be seen.[20] Children are more likely to present with fever, somnolence, convulsions, constipation, and abdominal pain.[19] When eosinophilic meningoencephalitis results in coma, a mortality rate of greater than 90% has been described despite corticosteroid administration.[21] Ocular angiostrongyliasis has been seen in about 1% of all reported cases. Ocular angiostrongyliasis occurs when the larva enters the anterior or posterior chamber; the exact mechanism of entry into the eye is unclear but has been thought to be secondary to travel along the retinal artery between the optic nerve and sheath. Usually, only 1 larva is present, and the symptoms include blurred vision, blindness, and pain.[14][22] Usually, eosinophilic meningitis is also present in these patients. Rarely, ocular involvement can manifest with symptoms of foreign body sensation, diplopia, blurred vision from the anterior chamber, and intravitreal invasion of larvae, respectively.[23][24][25][26] The specific CNS features of infection include new-onset severe headaches resistant to nonsteroidal anti-inflammatory therapy, classically described as “exploding” and lasting for up to a week. New-onset paresthesias, such as touch hypersensitivity or tingling and burning sensations, can occur in up to 40% of patients and last up to 2 weeks.[20] Shifting paresthesia is a notable characteristic, along with migratory pain in the trunk and limbs, as opposed to a dermatological distribution.[27] Sixth or seventh cranial nerve palsy may occur.

The specific CNS features of infection include new-onset severe headaches resistant to nonsteroidal anti-inflammatory therapy, classically described as “exploding” and lasting for up to a week. New-onset paresthesias, such as touch hypersensitivity or tingling and burning sensations, can occur in up to 40% of patients and last up to 2 weeks.[20] Shifting paresthesia is a notable characteristic, along with migratory pain in the trunk and limbs, as opposed to a dermatological distribution.[27] Sixth or seventh cranial nerve palsy may occur. Some patients may develop urinary retention, though the mechanism is unclear. Before CNS symptoms become prominent, changes usually start with the gastrointestinal tract, with nonspecific abdominal pain, nausea, and vomiting. This occurs due to the larval infiltration of the intestinal wall.[28] Larvae then circulate through the blood and ultimately penetrate the brain through the blood-brain barrier when the neurological symptoms occur. This period takes 1 to a few weeks, so patients may have a resolution of the initial gastrointestinal symptoms and be asymptomatic, or the gastrointestinal symptoms may persist during this time. Emesis can also occur due to meningeal involvement or gastrointestinal upset. More nonspecific symptoms include lethargy, low-grade fever, difficulty sleeping, and confusion. The physical examination of a patient with suspected angiostrongyliasis should consist of an abdominal examination and a complete neurological examination, which may reveal cranial nerve deficits, ataxia, and radiculitis. Ocular findings may include retinal edema, macular edema, pale optic discs, and alteration of the retinal pigment epithelia with delayed latency on visually evoked potentials.[14]

Laboratory Studies Diagnosis of neuroangiostrongyliasis is made on the grounds of clinical history, suggestive clinical features, and supporting laboratory findings. Clinical history should focus on travel to or from an endemic area, consumption of poorly cooked foods or raw vegetables contaminated with snail and slug components, including salad, crustaceans such as crab and shrimp, and insects, including caterpillars. Lumbar puncture is indicated in those with findings concerning for meningitis and encephalitis, with cerebrospinal fluid (CSF) results usually demonstrating pleocytosis (>5000 cell/mm3), elevated protein, and normal or low glucose.[18] Although not confirmatory, CSF eosinophilia, which usually exceeds 10% but can be as high as 70%, can aid diagnosis in the right clinical setting. Eosinophilia in the CSF is defined as 10 or more eosinophils per µL of CSF fluid or more than 10% of total CSF leukocytes with at least 6 in absolute count per µL of fluid.[29] CSF opening pressure and protein are usually elevated, with CSF leucocytosis typically ranging from 150 to 2000 cells/mm3.[30] Peripheral eosinophilia is often reported but does not correlate well with CSF eosinophilia or the clinical course. Even when blood eosinophil counts number more than 798 cells, there is a low positive predictive value (58.1%) but a high negative predictive (90.5%).[31] These predictive values demonstrate that peripheral eosinophilia’s most significant utility is ruling out A cantonensis infection when eosinophil counts are normal; however, eosinophilia in the CSF may not always be present during A cantonensis CNS infection.[32] Serological immunoassays such as dot blot enzyme-linked immunosorbent assay or western blot can aid the diagnosis but are not widely available. Polymerase chain reaction (PCR) and real-time PCR-based tests are reported to have good sensitivities, particularly with a higher percentage of CSF eosinophilia (>16%); these methods are not readily available outside dedicated centers or well-funded organizations.[33][32] The diagnostic immunoblot band is usually 29 kDa and is a reliable marker for diagnosis, with low sensitivity (55.6%) but high specificity (99.4%).[34] Imaging Studies

Serological immunoassays such as dot blot enzyme-linked immunosorbent assay or western blot can aid the diagnosis but are not widely available. Polymerase chain reaction (PCR) and real-time PCR-based tests are reported to have good sensitivities, particularly with a higher percentage of CSF eosinophilia (>16%); these methods are not readily available outside dedicated centers or well-funded organizations.[33][32] The diagnostic immunoblot band is usually 29 kDa and is a reliable marker for diagnosis, with low sensitivity (55.6%) but high specificity (99.4%).[34] Imaging Studies Brain imaging with computed tomography or magnetic resonance imaging (MRI) is generally not helpful in making the etiological diagnosis, given the nonspecific radiological findings.[35][36] Findings on MRI may include linear or nodular enhancement of the pia mater on T1-weighted images and fluid-attenuated inversion recovery sequences, with possible changes reflecting meningitis, encephalitis, or vasculitis.[35] Contrast enhancement may indicate hyperplastic and dilated vasculature. However, these features are nonspecific and are not pathognomonic for cerebral angiostrongyliasis.

The severity and duration of clinical manifestations are variable and dependent on the parasitic burden. Most patients have spontaneous resolution of symptoms with conservative measures. The goal is to decrease the meningeal inflammation, lower the intracranial pressure, and provide symptomatic relief of headaches. The early administration of steroids, such as prednisolone or dexamethasone, to depress the inflammatory reaction has been associated with decreasing the duration of headaches and the requirement for serial CSF drainage; given the lack of randomized trials in this stage, evidence for steroid use is largely in the role of supportive therapy.[37] Antihelminthic medications were traditionally not recommended due to the potential risk of an exaggerated inflammatory response to releasing antigens from dying parasites. Although the addition of antihelminthic therapy to steroids has not shown benefit in the outcome of treatment compared to steroids alone, anthelmintic therapy is safe and should be considered in patients with a high parasite load.[36][38] Ocular angiostrongyliasis requires laser treatment (photocoagulation) to immobilize or kill the larva before surgical removal. Repeated lumbar punctures do not appear to improve headache severity.[39]

Antihelminthic medications were traditionally not recommended due to the potential risk of an exaggerated inflammatory response to releasing antigens from dying parasites. Although the addition of antihelminthic therapy to steroids has not shown benefit in the outcome of treatment compared to steroids alone, anthelmintic therapy is safe and should be considered in patients with a high parasite load.[36][38] Ocular angiostrongyliasis requires laser treatment (photocoagulation) to immobilize or kill the larva before surgical removal. Repeated lumbar punctures do not appear to improve headache severity.[39] No official national guidelines for treatment have been established. However, from evidence-based studies, the following recommendations are generally followed. In centers established with angiostrongyliasis molecular diagnostic methods, a real-time PCR test can be performed on CSF fluid that detects deoxyribonucleic acid from A cantonensis. If the PCR is negative during early infection, a repeat PCR and lumbar puncture should be performed if there is an ongoing suspicion of infection. Serological testing against antibodies in the serum or CSF is not recommended as results are difficult to interpret due to the risk of false positives and a low positive predictive value in low-endemic areas.[32] If added, albendazole may provide benefits but should be used with steroids to dampen the intense inflammatory response created by the dying parasites. Careful attention should be paid to adequate glycemic control in diabetic individuals as recommended by guidelines for diagnosing and treating neuroangiostrongyliasis.[40] However, evidence for this is limited and is based on the possible hypoglycemia that may occur concurrently with low glucose in the CSF.

The diagnosis of angiostrongyliasis is dependent on a heightened suspicion for patients who have likely been exposed to the nematode during the previous few weeks, which can extend up to 6 weeks prior. Other infections that can cause eosinophilic meningitis include gnathostomiasis and baylisascariasis. Gnathostomiasis usually presents with radicular pain, nontraumatic bloody or xanthochromic CSF, with brain imaging revealing subarachnoid or intracerebral hemorrhage. Gnathostomiasis is associated with consuming undercooked fish, poultry, or snake meat, while the consumption of parasites, usually in children who ingest soil, causes baylisascariasis (Baylisascaris procyonis) secondary to eggs frequently transmitted in raccoon feces.[41][42] Imaging for gnathostomiasis may sometimes reveal myelitis, but this is not found in the case of A cantonensis. Cysticercosis caused by Taenia solium or other diseases caused by lung flukes such as schistosomiasis and paragonimiasis are other important differentials. Coccidioidomycosis is also associated with eosinophilic meningitis.[43] Noninfectious causes of eosinophilic leptomeningeal enhancement include non-Hodgkin lymphoma, myeloproliferative disorders, disseminated glioblastoma, and paraneoplastic manifestation from bronchogenic carcinoma.[44] Drugs associated with eosinophilic meningitis include trimethoprim-sulphamethoxazole, ciprofloxacin, ibuprofen, intraventricular vancomycin, and gentamicin.[45] Encephalopathy and neurological deficits have been reported to be associated with idiopathic hypereosinophilic syndrome.[46]

The prognosis depends on the timing of the correct diagnosis, as eosinophilic meningitis is rare and requires reasonable clinical suspicion to suspect A cantonensis and appropriate CSF or molecular findings. Most cases of infection are self-limiting, including meningitis; other times, depending on the disease burden, this condition may be fatal or induce long-term neurological disability.[19] Results from studies in mice with neuroangiostrongyliasis demonstrate a loss of weight, reduced movement, and speed control compared to those without angiostrongyliasis.[47] Overall, global surveillance of this disease is lacking, and due to the limited diagnostic testing and poor general awareness among many clinicians, it is difficult to quantify the outcomes.

Complications may include permanent blindness, ongoing focal neurological deficits, coma, and death from eosinophilic meningitis or meningoencephalitis. Other long-term complications include persisting radicular and neuropathic pain syndromes, fatigue, persistent nerve palsies, and paresthesia.[48] Given the lack of studies analyzing long-term data due to the rarity of angiostrongyliasis, further complications are difficult to elucidate. Managing these sequelae is largely supportive based on the severity of disabilities with a multidisciplinary team approach.

Angiostrongyliasis in humans has been associated with consuming the intermediate and paratenic hosts of the A cantonensis species. Locally confirmed cases should be reported to public health officials to investigate and decrease further consumption of infected intermediate and paratenic hosts, thereby reducing exposure to the source if there is a local transmission. Many cases occur in travelers who often visit endemic areas and are exposed through the consumption of high-risk foods containing A cantonensis. These individuals must be aware of the undercooked consumption of crabs, snails, slugs, and prawns. Since the risk of infection occurs from ingesting the intermediate and paratenic hosts, ingesting raw snails or slugs, crabs, and shrimp should be avoided. Additionally, raw snails can be accidentally included in uncooked foods, including salads. Care should be taken in food preparation, such as cooking and boiling foods before consumption, refrigeration, appropriate washing and preparation of salads, and careful handwashing.[49]

A high index of clinical suspicion is most important in diagnosing A cantonensis meningitis. A patient with eosinophilic meningitis should always be further investigated for A cantonensis infection. The possible clinical exposure, especially travel to endemic areas, followed by acute or subacute meningitis, should raise suspicion. High-risk foods, including raw vegetables and salads, crustaceans, and insects from endemic areas, should increase angiostrongyliasis pre-test probability on history taking. Heightened CSF eosinophilia should point to the diagnosis, and molecular testing, where possible, should be performed in these instances. The key to treatment is supportive management with a focus on addressing symptoms.

To enhance patient-centered care, outcomes, and patient safety in Angiostrongylus cantonensis infection, a highly coordinated interprofessional approach is essential. Early diagnosis is critical to improving prognosis, requiring clinicians to maintain a high index of suspicion, especially in nonendemic areas. Infectious disease specialists are pivotal in guiding differential diagnoses and recommending optimal diagnostic and treatment strategies based on clinical, CSF, blood, and imaging findings. Ophthalmologists may be involved in managing ocular angiostrongyliasis through laser therapy and surgical removal of larvae. To address long-term complications, rehabilitation involving occupational and physical therapists, as well as exercise physiologists, is critical for managing persistent neurological deficits. Patients with visual impairment need ongoing care from optometrists and ophthalmologists, while psychological services support those experiencing mental health challenges due to lingering symptoms. Social workers facilitate post-discharge transitions, ensuring patients receive community services to help with daily living activities. This collaborative team approach is particularly vital for improving outcomes in a rare, often underrecognized condition like A cantonensis meningitis, especially in developed nations where awareness may be limited.