Introduction
Changes in climate, ecosystems, global food trade, and human dietary habits have altered the epidemiology and geographic distribution of foodborne and zoonotic parasitic infections, contributing to the emergence and re-emergence of helminth infections, including angiostrongyliasis (Ortiz et al. Reference Ortiz, Uys, Seguino and Thomas2024). Among these infections, Angiostrongylus cantonensis (the rat lungworm) has received increasing attention because of its expanding geographic range and growing recognition in humans (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022). The parasite is maintained in a zoonotic cycle involving rodents as definitive hosts and gastropods as intermediate hosts, while various paratenic hosts, including freshwater prawns, crabs, and frogs, can harbour infective larvae (Capinera and Walden Reference Capinera and Walden2013; Kim et al. Reference Kim, Hayes, Yeung and Cowie2014). Humans become accidental hosts through ingestion of raw or undercooked intermediate or paratenic hosts or fresh produce contaminated with infective third-stage larvae (L3) (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Prociv and Carlisle Reference Prociv and Carlisle2001; Turck et al. Reference Turck, Fox and Cowie2022). Although historically associated with tropical and subtropical regions, human angiostrongyliasis is increasingly recognized outside traditional endemic areas, including Europe and North America (Bruschi Reference Bruschi2023; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Morgan et al. Reference Morgan, Modry, Paredes-Esquivel, Foronda and Traversa2021). This expansion has been linked to environmental change, globalisation of food supply chains, host range expansion, and changing patterns of food consumption and travel (Robertson et al. Reference Robertson, Sprong, Ortega, van der Giessen and Fayer2014; York et al. Reference York, Butler and Lord2014). Clinically, A. cantonensis most commonly causes eosinophilic meningitis, which may result in severe neurological complications (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). In addition, Angiostrongylus costaricensis causes abdominal angiostrongyliasis and represents an important but clinically distinct form of human disease. This review summarizes the past, present, and future of human angiostrongyliasis, with emphasis on epidemiological expansion, advances in diagnosis and treatment, and emerging research priorities for prevention and control.
Angiostrongylus spp.
Human angiostrongyliasis is caused mainly by Angiostrongylus cantonensis and Angiostrongylus costaricensis, which differ in tissue tropism, clinical manifestations, and geographic distribution despite sharing broadly similar zoonotic transmission cycles. A. cantonensis is the principal cause of neuroangiostrongyliasis and eosinophilic meningitis, whereas A. costaricensis causes abdominal angiostrongyliasis, characterized by eosinophilic inflammation of the intestinal wall and mesenteric vasculature (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). In A. cantonensis, adults inhabit the pulmonary arteries of rodents, whereas humans are accidental hosts in which larvae migrate mainly to the CNS and cause eosinophilic meningitis or meningoencephalitis (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Turck et al. Reference Turck, Fox and Cowie2022). A. costaricensis is predominantly distributed in Central and South America; adults inhabit mesenteric and ileocolic arteries of rodents, while human infection causes abdominal disease characterized by eosinophilic intestinal and vascular inflammation and may lead to thrombosis, ischemia, perforation, or haemorrhage (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Spratt Reference Spratt2015; Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). The epidemiological profiles of the two species also differ. A. cantonensis has expanded across Asia, the Pacific, the Americas, and increasingly Europe, whereas human A. costaricensis infection remains largely concentrated in Latin America (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Morgan et al. Reference Morgan, Modry, Paredes-Esquivel, Foronda and Traversa2021; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Valente et al. Reference Valente, Robles and Diaz2020). Diagnosis also differs between the two infections. Neuroangiostrongyliasis is assessed using clinical and epidemiological findings, CSF eosinophilia, serology, and, where available, molecular detection of parasite DNA. In contrast, abdominal angiostrongyliasis is frequently diagnosed by combining clinical and imaging findings with peripheral eosinophilia, histopathology, and detection of adult worms, eggs, or larvae in surgical or biopsy specimens (Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). The presence of multiple zoonotic Angiostrongylus species and increasing evidence of genetic diversity further support species-level identification in epidemiological and clinical investigations (Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024; Spratt Reference Spratt2015).
Epidemiology
Global distribution and trends
The global distribution of human angiostrongyliasis is closely linked to the distribution of definitive rodent hosts and gastropod intermediate hosts and is further modified by climate, trade, land-use change, and human behaviour. A. cantonensis remains endemic in many tropical and subtropical regions, particularly Southeast Asia and the Pacific Islands (Ansdell and Wattanagoon Reference Ansdell and Wattanagoon2018; Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Lv et al. Reference Lv, Zhang, Steinmann and Zhou2008). However, autochthonous transmission has increasingly been recognized outside these historical foci, including the Americas, Europe, and parts of Africa. The expansion of invasive gastropods, particularly Achatina fulica and Pomacea canaliculata, has facilitated the establishment of new transmission foci (Lv et al. Reference Lv, Zhang, Liu, Hu, Yang, Steinmann, Chen, Wang, Utzinger and Zhou2009; Silva et al. Reference Silva, Thiengo, Sierpe Jeraldo, Rego, Silva, Rodrigues and Gomes2022; Wang et al. Reference Wang, Wu, Wei, Owen and Lun2012; Yang et al. Reference Yang, Z-D and Lun2013). In Europe, sporadic human infections and established parasite populations have now been documented, while North America has also experienced geographic range expansion (Bruschi Reference Bruschi2023; Galán-Puchades et al. Reference Galán-Puchades, Gómez-Samblás, Osuna, Sáez-Durán, Bueno-Marí and Fuentes2023; Morgan et al. Reference Morgan, Modry, Paredes-Esquivel, Foronda and Traversa2021; York et al. Reference York, Creecy, Lord and Caire2015). The observed increase in reported infections likely reflects both genuine emergence and improved clinical recognition and molecular confirmation, although the overall burden remains underestimated because of underdiagnosis and limited access to confirmatory testing (Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). Several interacting factors contribute to this expansion, including warmer and more humid conditions favouring gastropod hosts, movement of infected animals and contaminated agricultural products, dietary exposure to raw vegetables or inadequately cooked food, and greater use of molecular diagnostics such as PCR (Qvarnstrom et al. Reference Qvarnstrom, Sullivan, Bishop, Hollingsworth and da Silva2007, Reference Qvarnstrom, Xayavong, da Silva, Park, Whelen, Calimlim, Sciulli, Honda, Higa, Kitsutani, Chea, Heng, Johnson, Graeff-Teixeira, Fox and da Silva2016; York et al. Reference York, Butler and Lord2014). Rodents maintain transmission in both urban and rural environments, while contamination of fresh produce by infected gastropods or their mucus represents an important but often underrecognized route of human infection (Qvarnstrom et al. Reference Qvarnstrom, Xayavong, da Silva, Park, Whelen, Calimlim, Sciulli, Honda, Higa, Kitsutani, Chea, Heng, Johnson, Graeff-Teixeira, Fox and da Silva2016; Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008).
Recent global Angiostrongylus cases
Historical records demonstrate long-standing transmission in regions such as Hawaii and Australia. The first recognized epidemic of eosinophilic meningitis in Hawaii occurred in 1958, and A. cantonensis has subsequently become established in several parts of the region (Wallace Reference Wallace2013). In Australia, sporadic cases have been reported since the late 1950s, with increasing autochthonous transmission from the 1970s onward (Prociv and Carlisle Reference Prociv and Carlisle2001). Europe represents a more recent area of emergence (Paredes-Esquivel et al. Reference Paredes-Esquivel, Foronda, Dunavan and Cowie2023). A. cantonensis was detected in Rattus rattus in Tenerife in 2010 (Foronda et al. Reference Foronda, López-González, Miquel, Torres, Segovia, Abreu-Acosta, Casanova, Valladares, Mas-Coma, Bargues and Feliu2010), subsequently identified in North African hedgehogs in Mallorca in 2018 (Paredes-Esquivel et al. Reference Paredes-Esquivel, Sola, Delgado-Serra, Puig Riera, Negre, Miranda and Jurado-Rivera2019), and detected in potential intermediate hosts in the European Mediterranean region (Jaume-Ramis et al. Reference Jaume-Ramis, Martínez-Ortí, Delgado-Serra, Bargues, Mas-Coma, Foronda and Paredes-Esquivel2023). The first confirmed establishment in continental Europe was reported in Valencia, Spain, in 2022, where adult worms were recovered from sewer rats (Galán-Puchades et al. Reference Galán-Puchades, Gómez-Samblás, Osuna, Sáez-Durán, Bueno-Marí and Fuentes2023). A confirmed autochthonous human case was reported in Paris in 2016 in a patient without recent travel outside France, although the source of infection remained unknown (Federspiel et al. Reference Federspiel, Skovmand and Skarphedinsson2020). In Central and South America, the epidemiology includes both A. cantonensis and A. costaricensis. A. costaricensis remains predominantly restricted to the Neotropical region, with human disease reported from multiple Latin American countries (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Valente et al. Reference Valente, Robles and Diaz2020). Unlike A. cantonensis, A. costaricensis remains geographically restricted, although environmental and demographic changes could influence its future distribution (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024). Asia remains a major centre of Angiostrongylus diversity (Pandian et al. Reference Pandian, Najer and Modrý2023). Molecular studies have highlighted the close relationship between A. cantonensis and Angiostrongylus malaysiensis and have demonstrated the possibility of co-infection (Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024; Kaenkaew et al. Reference Kaenkaew, Chan, Saralamba, Ruangsittichai, Chaisiri, Charoennitiwat, Intapan, Maleewong and Thaenkham2024). Other species, such as A. mackerrasae, remain under investigation because human infection has not been confirmed (Mackerras and Sandars Reference Mackerras and Sandars1955; Prociv and Carlisle Reference Prociv and Carlisle2001; Spratt Reference Spratt2015). Together, these findings demonstrate the changing epidemiology and increasing diversity of zoonotic Angiostrongylus species (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024).
Clinical presentation
Human angiostrongyliasis presents with a clinical spectrum that varies according to the infecting species, parasite burden, and host factors such as age and immune status. While the majority of infections are self-limited, severe and occasionally fatal outcomes can occur, particularly in vulnerable populations (Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022).
Incubation period and general symptoms
The incubation period for A. cantonensis infection averages 1–3 weeks following ingestion of infective larvae, but has been documented to range from as little as one day to more than six weeks, depending on the infectious dose and host immune response (Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). The illness typically lasts between 2 and 8 weeks but can persist longer in some patients (Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). The most common clinical presentation is eosinophilic meningitis, characterised by severe and often global headache, neck stiffness, nausea, vomiting, and paraesthesia (abnormal skin sensations such as tingling or pain). Low-grade fever may be present, though it is not a universal finding (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009).
Spectrum of severity and mortality
Disease ranges from mild or asymptomatic infection to severe neurological involvement. Serious complications include altered mental status, seizures, coma, cranial nerve palsies, radiculomyelitis, and ocular involvement (Cowie Reference Cowie2017). Young children, particularly those younger than five years, may be at increased risk of severe neurological injury and death (Evans-Gilbert et al. Reference Evans-Gilbert, Lindo, Henry, Brown and Christie2014). Overall mortality is generally below 2%, although rates of 5–10% have been reported in severe outbreaks and in patients with brainstem involvement or heavy parasite burdens (Cowie Reference Cowie2017; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Slom et al. Reference Slom, Cortese, Gerber, Jones, Holtz, Lopez, Zambrano, Sufit, Sakolvaree, Chaicumpa, Herwaldt and Johnson2002).
Disease caused by A. costaricensis
In contrast to A. cantonensis, infection with A. costaricensis results in abdominal angiostrongyliasis, a syndrome that primarily affects children and young adults in endemic areas of the Americas (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). The incubation period is less precisely defined but is thought to range from several weeks to several months, possibly up to one year (Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). Clinical manifestations typically mimic acute appendicitis, with right lower quadrant abdominal pain, fever, nausea, vomiting, and a palpable mass, often localised to the ileocecal region (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). In some cases, larvae penetrate the mesenteric arteries, where they mature into adults and cause arteritis, thrombosis, infarction, or gastrointestinal haemorrhage. Eggs deposited by adult worms become lodged in the capillary bed of the intestinal wall, triggering an eosinophilic granulomatous inflammatory reaction that can progress to intestinal obstruction, perforation, or peritonitis (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). Peripheral eosinophilia is common, and imaging studies (ultrasound or CT) may reveal a thickened bowel wall or an inflammatory mass. Definitive diagnosis often requires histopathological examination of surgical specimens, as serological tests are not widely available in endemic settings (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). Deaths have been reported, and recurrent episodes of illness may occur over several months (Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). Treatment generally consists of supportive care and, when indicated, surgical resection of the affected segment; corticosteroids are sometimes used to temper the inflammatory response, but the role of anthelmintics remains uncertain and is generally avoided due to the potential for exacerbating local tissue damage (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023).
Foodborne transmission and epidemiological patterns
Foodborne transmission is the dominant route of human infection. A landmark review by Wang et al. (Reference Wang, Lai, Zhu, X-G and Lun2008) documented at least 2,827 cases of human angiostrongyliasis worldwide as of 2008, overwhelmingly associated with the ingestion of raw or undercooked intermediate hosts (snails and slugs), paratenic hosts (e.g., freshwater prawns), or contaminated vegetables. The same review noted that among these documented cases, Thailand accounted for the largest number (1,337 cases), followed by China (including Hong Kong and Taiwan, 769 cases), Tahiti (256), the United States (Hawaii and Samoa, 116), and Cuba (114) (Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). The global distribution of cases has since expanded further, with autochthonous transmission now confirmed in Europe and increasing case numbers reported in the Americas (Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; York et al. Reference York, Creecy, Lord and Caire2015).
Co-infections with other foodborne parasites
Because A. cantonensis is transmitted through the same dietary routes as other foodborne helminths, co-infections can and do occur. This is particularly relevant in Southeast Asia, where multiple zoonotic parasites overlap geographically (Lv et al. Reference Lv, Zhang, Steinmann, Zhou and Utzinger2010). A. cantonensis, Gnathostoma spinigerum, and Paragonimus westermani are all acquired through ingestion of undercooked freshwater animals such as snails, crabs, and shrimp (Lv et al. Reference Lv, Zhang, Steinmann, Zhou and Utzinger2010). Co-infection is most notable in Thailand, where both A. cantonensis and G. spinigerum are recognised causes of eosinophilic meningitis and radiculomyelitis (Schmutzhard et al. Reference Schmutzhard, Boongird and Vejjajiva1988). A study of 44 patients with CNS parasitic infections at a hospital in Bangkok found that both organisms were responsible for eosinophilic meningitis cases, with Gnathostoma additionally causing encephalitis, myelitis, and subarachnoid haemorrhage, while Angiostrongylus predominantly presented with meningitis (Schmutzhard et al. Reference Schmutzhard, Boongird and Vejjajiva1988). When co-infection occurs, the clinical picture may be more severe and diagnostically challenging (Schmutzhard et al. Reference Schmutzhard, Boongird and Vejjajiva1988). Patients with dual infections may present with aggravated or overlapping symptoms – for example, more severe headache, more pronounced neurological deficits, or mixed syndromes of meningitis and radiculomyelitis – compared with infection by a single parasite (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009). Distinguishing between eosinophilic meningitis caused by Angiostrongylus versus Gnathostoma is difficult on clinical grounds alone, necessitating serological or molecular differentiation (Intapan et al. Reference Intapan, Khotsri, Kanpittaya, Chotmongkol, Sawanyawisuth and Maleewong2010).
Diagnostic considerations in suspected cases
Given the potential for severe outcomes and diagnostic complexity, a high index of clinical suspicion is essential. Patients presenting with eosinophilic meningitis, particularly those with a history of residence in or travel to endemic areas, consumption of raw or undercooked freshwater products, or exposure to snails or slugs, should be evaluated for angiostrongyliasis (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009). The minimum diagnostic evaluation should include peripheral blood eosinophil count and lumbar puncture for cerebrospinal fluid (CSF) analysis, where eosinophilic pleocytosis (typically >10% eosinophils) is the hallmark finding (Ansdell and Wattanagoon Reference Ansdell and Wattanagoon2018; Graeff-Teixeira et al. Reference Graeff-Teixeira, Sawanyawisuth, Lv, Sears, Rodríguez, Álvarez, Arias, Schultz, Rojas, Jacob, Jarvi and Kramer2023). Confirmatory testing, where available, includes serological assays (ELISA, immunoblot) and molecular methods such as real-time PCR on CSF (Ansdell and Wattanagoon Reference Ansdell and Wattanagoon2018; Qvarnstrom et al. Reference Qvarnstrom, Xayavong, da Silva, Park, Whelen, Calimlim, Sciulli, Honda, Higa, Kitsutani, Chea, Heng, Johnson, Graeff-Teixeira, Fox and da Silva2016). Given that immunocompromised patients may present atypically and can deteriorate more rapidly, prompt diagnosis and early initiation of supportive care, including corticosteroids with or without anthelmintic therapy, are critical to reducing the risk of permanent neurological sequelae and death (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021; Cong et al. Reference Cong, Yu, Chen, Qin, Huang, Gao, D-F and Liu2025).
Transmission and life cycle
Angiostrongylus cantonensis requires a mammalian definitive host and a gastropod intermediate host to complete its life cycle. Rats, particularly Rattus norvegicus and Rattus rattus, serve as the principal definitive hosts. After ingestion of infective L3 larvae, the prepatent period is approximately 42–45 days (Mackerras and Sandars Reference Mackerras and Sandars1955). Adult worms reside in the pulmonary arteries, where eggs hatch in the pulmonary capillaries and release L1 larvae. These larvae migrate to the gastrointestinal tract and are excreted in faeces (da Silva and Morassutti Reference da Silva and Morassutti2021). Gastropods acquire L1 by ingestion, and larvae develop through L2 to infective L3 within molluscan tissues. Infected gastropods may contain large numbers of L3, which are also transmitted to paratenic hosts such as freshwater prawns, crabs, frogs, and monitor lizards (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Wallace and Rosen Reference Wallace and Rosen1969). Rats become infected by ingesting infected gastropods or paratenic hosts. The L3 penetrate the intestinal wall, migrate to the CNS, develop into young adults, and subsequently migrate to the pulmonary arteries, where they mature and reproduce (Barratt et al. Reference Barratt, Chan, Sandaradura, Malik, Spielman, Lee, Marriott, Harkness, Ellis and Stark2016; Turck et al. Reference Turck, Fox and Cowie2022). In humans, the larvae migrate to the CNS but do not normally complete their life cycle, and their death induces eosinophilic inflammation and neurological disease (Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022). A. costaricensis has a related but distinct cycle. Gastropods serve as intermediate hosts and rodents as definitive hosts, with adult worms developing mainly in mesenteric and ileocolic arteries (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). This difference in definitive-host localisation and tissue tropism explains the abdominal rather than neurological presentation of infection. Species-specific differences in natural history also support molecular identification in epidemiological and diagnostic investigations (Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). A comparison of the life cycles of both species is illustrated in Figure 1.
Comparative life cycles of Angiostrongylus cantonensis and Angiostrongylus costaricensis.
Adult A. cantonensis reside predominantly in the pulmonary arteries of definitive rodent hosts, primarily Rattus spp., whereas adult A. costaricensis are found mainly in the mesenteric and ileocolic arteries of rodent definitive hosts. In both species, eggs hatch in host tissues and release first-stage larvae (L1), which are passed in the faeces and ingested by gastropod intermediate hosts (snails and slugs). Within gastropods, L1 develop through the second stage (L2) to infective third-stage larvae (L3). Rodents acquire infection by ingesting infected gastropods, whereas humans are accidental hosts and may become infected through consumption of raw or undercooked gastropods or raw vegetables contaminated with infected gastropods or their tissues. In A. cantonensis, ingested L3 penetrate the intestinal wall and migrate to the central nervous system, where they develop before returning to the pulmonary arteries and maturing into adults in the natural definitive host. In humans, the normal life cycle is not completed, and larvae predominantly localize in the central nervous system, causing neuroangiostrongyliasis, most commonly presenting as eosinophilic meningitis or meningoencephalitis. In A. costaricensis, L3 migrate through lymphatic and vascular pathways to the mesenteric and ileocolic vessels, where they mature into adults and reproduce in the natural definitive host. In humans, infection primarily involves the mesenteric vasculature and intestinal tissues and results in abdominal angiostrongyliasis. The figure highlights the shared transmission cycle and the major differences in definitive-host localisation and tissue tropism between the two species.
Figure 1. Long description
The flowchart is divided into two main panels.
Left Panel: Angiostrongylus cantonensis (Neuroangiostrongyliasis).
1. At the top, a rat and a diagram of lungs represent the definitive host where adult worms reside in pulmonary arteries. Eggs hatch in lungs and L 1 larvae are coughed up and swallowed.
2. Red arrows point to L 1 larvae passed in rat feces.
3. Blue arrows indicate L 1 larvae ingested by intermediate hosts, a snail and a slug.
4. Larvae develop within the gastropod from L 1 to L 2 to L 3.
5. Infective L 3 larvae are present in the mucus or tissues of the snail or slug.
6. A plate of leafy vegetables with a snail illustrates human infection via ingestion of raw gastropods or contaminated produce.
7. An illustration of a human head shows L 3 larvae penetrating the intestinal wall and migrating to the C N S (brain and spinal cord) to mature.
Right Panel: Angiostrongylus costaricensis (Abdominal angiostrongyliasis).
1. At the top, a rodent and a diagram of the intestine represent the definitive host where adult worms reside in mesenteric arteries. Eggs hatch in vessels and L 1 larvae pass into the intestinal lumen.
2. Green arrows point to L 1 larvae passed in rodent feces.
3. L 1 larvae are ingested by snails and slugs.
4. Larvae develop from L 1 to L 2 to L 3 within the gastropod.
5. Infective L 3 larvae are found in gastropod tissues.
6. A human figure holding their abdomen indicates infection via contaminated food.
7. An inset shows L 3 larvae migrating to mesenteric vessels and maturing.
A legend at the bottom defines blue/green arrows as the life cycle in nature and red arrows as infection to definitive or human hosts. Key points boxes summarize that A. cantonensis targets the C N S while A. costaricensis targets the abdomen.
Diagnosis
Diagnosis of human angiostrongyliasis remains challenging and rests on a combination of clinical suspicion, epidemiological exposure history, and supportive laboratory findings. Cases are globally underreported, even in well-known endemic regions such as Southeast Asia and the Caribbean, largely due to nonspecific symptoms and limited access to confirmatory testing. This diagnostic gap is particularly consequential for vulnerable populations – including children, pregnant women, and immunocompromised individuals – where delayed diagnosis can lead to poor outcomes (Ansdell and Wattanagoon Reference Ansdell and Wattanagoon2018). A diagnosis of A. cantonensis infection should be suspected when a patient presents with symptoms suggestive of meningitis but cerebrospinal fluid (CSF) analysis reveals eosinophilic pleocytosis (typically >10% eosinophils), accompanied by peripheral blood eosinophilia (>5%), in the context of a compatible exposure history. CSF microscopy can rapidly identify eosinophilic pleocytosis and, rarely, larvae; however, direct larval detection has low sensitivity because parasite burden in the CNS is often limited. Thus, CSF eosinophilia remains a more useful early supportive finding (Ansdell and Wattanagoon Reference Ansdell and Wattanagoon2018; Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009). Polymerase chain reaction (PCR) is an important method for direct detection of current infection when microscopy is unrevealing. Diagnostic PCR assays have targeted conserved regions such as the Angiostrongylus 18S rRNA gene and the internal transcribed spacer 1 (ITS-1) region. Real-time PCR assays for A. cantonensis have been developed and evaluated using cerebrospinal fluid (CSF) specimens (Qvarnstrom et al. Reference Qvarnstrom, Xayavong, da Silva, Park, Whelen, Calimlim, Sciulli, Honda, Higa, Kitsutani, Chea, Heng, Johnson, Graeff-Teixeira, Fox and da Silva2016; Wilkins et al. Reference Wilkins, Qvarnstrom, Whelen, Saucier, da Silva and Eamsobhana2013). More recently, the AcanR3990 real-time PCR assay, developed using a highly repetitive genomic target identified through bioinformatic analysis, demonstrated substantially improved analytical sensitivity compared with the ITS1-based assay while maintaining high specificity. In a study of archived CSF specimens, AcanR3990 detected all previously confirmed A. cantonensis infections and additionally identified a subset of clinically suspected cases that had tested negative by the ITS1 assay, highlighting its potential value for sensitive and early molecular diagnosis of neuroangiostrongyliasis (Sears et al. Reference Sears, Qvarnstrom, Dahlstrom, Snook, Kaluna, Baláž, Feckova, Šlapeta, Modry, Jarvi and Nutman2021). A significant limitation of species-specific PCR is the potential for false-negative results when infections are caused by rare or newly emerging Angiostrongylus species. For this reason, the use of broad-range primers targeting conserved loci across the genus Angiostrongylus, followed by sequencing for species-level identification, is recommended. Universal primers designed against consensus sequences of the 18S rRNA gene and ITS-1 region have shown particular utility when routine species-specific PCR yields negative results and have proven effective in detecting a broad range of species, including rare ones such as Angiostrongylus mackerrasae (Chan et al. Reference Chan, Kaenkaew, Pakdee and Thaenkham2024). When direct detection of larvae or parasite DNA is unsuccessful, antibody-based and antigen-based serological assays provide valuable confirmatory evidence. These methods rely on detecting host antibodies against parasite-derived proteins, such as excretory-secretory (E/S) antigens, or on capturing circulating parasite antigens directly from clinical specimens (Chye et al. Reference Chye, Lin, Chen, L-Y and Yen2004; Zhang et al. Reference Zhang, Liu, Wu, Mo, Shen, Chen and Li2012). Immunofluorescence assays (IFAs) and enzyme-linked immunosorbent assays (ELISA) have been used for detecting antibodies in both serum and CSF. IFAs can detect antibodies indicating current or past infection by incubating Angiostrongylus antigens with patient serum and then adding fluorescently tagged secondary antibodies; fluorescence microscopy reveals the presence of specific antibodies. However, serological responses may take up to 3 weeks to develop, limiting utility for acute diagnosis and making these tests more applicable for chronic infection or retrospective epidemiological analysis (Murphy and Johnson Reference Murphy and Johnson2013). ELISA-based testing has demonstrated improved utility. The recombinant 31-kDa glycoprotein antigen from A. cantonensis has been used to develop indirect ELISA and immunoblot (EITB) assays. Early assays using crude antigens showed variable specificity and sensitivity, whereas purified 31-kDa antigen substantially improved specificity (Eamsobhana and Yong Reference Eamsobhana and Yong2009; Nuamtanong Reference Nuamtanong1996). More recent work has developed an indirect ELISA using an E/S antigen preparation that demonstrated 86% sensitivity and 100% specificity when applied to human serum (Eamsobhana et al. Reference Eamsobhana, Tungtongchitr, Wanachianwanin, Boonyong and Yong2023). Antigen capture assays represent an important complementary approach. Antigen-capture approaches, including sandwich ELISA and immuno-PCR, can detect circulating parasite antigens and may facilitate diagnosis of active infection, although they remain largely investigational (Chen et al. Reference Chen, Wang, Ai, Yan, Peng and Zhang2011; Chye et al. Reference Chye, Lin, Chen, L-Y and Yen2004). These antigen-based approaches have the advantage of detecting active infection rather than past exposure, and they hold particular promise for monitoring treatment response. However, these assays have not been widely validated or commercialised for routine clinical use (Wilkins et al. Reference Wilkins, Qvarnstrom, Whelen, Saucier, da Silva and Eamsobhana2013). Recent efforts have focused on developing rapid, point-of-care diagnostic platforms that can be deployed in resource-limited settings. Lateral-flow immunochromatographic tests have emerged as a practical alternative to laboratory-based serology. The AcQuickDx Test, assembled with purified 31-kDa glycoprotein as the diagnostic antigen, demonstrated sensitivity of 100% and specificity of 98.72% for detecting anti-A. cantonensis antibodies in serum from serologically confirmed cases; the test yields visually interpreted results and possesses a long shelf-life at room temperature, making it suitable for remote settings (Eamsobhana et al. Reference Eamsobhana, Tungtrongchitr, Wanachiwanawin and Yong2018). A separate ICT developed using recombinant A. cantonensis galectin-2 (rAcGal2) protein showed sensitivity and specificity of 92.0% and 97.1% in serum, and 82.0% and 97.1% in simulated whole-blood samples, and also successfully detected antibodies in 12 of 16 CSF samples from eosinophilic meningitis cases (Boonroumkaew et al. Reference Boonroumkaew, Sadaow, Kanchanangkul, Rodpai, Sanpool, Intapan, Blair and Maleewong2025). An antigen-detection version of the ICT, designated AcAgQuickDx, uses anti-31-kDa A. cantonensis antibody as the capture reagent and has demonstrated the capacity for rapid detection of active/acute infection in CSF and serum, with excellent specificity and no cross-reactivity with other parasitic infections (Eamsobhana et al. Reference Eamsobhana, Tungtongchitr, Wanachianwanin, Boonyong and Yong2023). While ICTs offer ease of use and field-deployability, they currently cannot distinguish acute from past infection when configured for antibody detection alone (Boonroumkaew et al. Reference Boonroumkaew, Sadaow, Kanchanangkul, Rodpai, Sanpool, Intapan, Blair and Maleewong2025). A recombinase polymerase amplification lateral flow assay (RPA-LFA) targeting the ITS-1 gene of A. cantonensis has been developed for detecting parasite DNA. When compared with quantitative PCR, the RPA-EXO format detected as few as 25 copies μL−1, while the RPA-LFA format reliably amplified down to 50 copies μL−1, making these assays somewhat less sensitive than qPCR (which detected ~13 copies μL−1) at very low DNA concentrations. Nevertheless, RPA-based methods offer significant practical advantages: they are faster (10–30 minutes), can be performed at a range of ambient temperatures (25–45 °C), do not require thermocycling equipment, and are more stable under field conditions. Currently validated on A. cantonensis only, further development is needed to extend detection to other Angiostrongylus species (Jarvi et al. Reference Jarvi, Atkinson, Kaluna, Snook and Steel2021). Recent work has established a sandwich dot-immunogold filtration assay (AcDIGFAAg) for detecting active neuroangiostrongyliasis, using anti-A. cantonensis polyclonal antibody on a nitrocellulose membrane as a capture agent and colloidal gold-labelled anti-31-kDa antibody for detection. This approach complements existing ICT formats and further demonstrates the versatility of the 31-kDa antigen as a diagnostic target across multiple platforms (Eamsobhana et al. Reference Eamsobhana, Tungtrongchitr, Yong, Prasartvit, Wanachiwanawin and Gan2021). Diagnosis of abdominal angiostrongyliasis caused by A. costaricensis is particularly challenging because clinical features overlap with acute surgical abdomen, and the parasite is rarely detected in stool or blood. A definitive diagnosis is often made postoperatively through histopathological examination of resected intestinal tissue, where sections of adult worms, eggs, or granulomatous inflammation with abundant eosinophils can be observed in the submucosa and mesenteric vessels (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). Serological tests, including ELISA using crude or recombinant antigens, have been developed for A. costaricensis, but they are not commercially available, and cross-reactivity with A. cantonensis and other helminths can occur (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). Molecular methods such as PCR on tissue or blood samples are promising but remain largely confined to research settings. In endemic areas, a high index of suspicion is required for timely diagnosis, as delayed recognition can lead to bowel perforation, peritonitis, and sepsis. Imaging studies (abdominal ultrasound or CT) may reveal a right lower quadrant inflammatory mass or thickened ileocecal wall, which, in the presence of peripheral eosinophilia and appropriate exposure history, should prompt consideration of A. costaricensis infection (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). The major diagnostic approaches for neuroangiostrongyliasis and abdominal angiostrongyliasis, together with their respective advantages and limitations, are summarized in Table 1.
Diagnostic approaches for human angiostrongyliasis and their primary application to Angiostrongylus species
Table 1. Long description
The table consists of five columns and nineteen rows of diagnostic data.
* C S F microscopy (wet mount/Giemsa/Wright stain): Primary application A. cantonensis. Targets direct visualization of larvae and C S F eosinophilia. Advantages: Rapid, inexpensive. Limitations: Low sensitivity.
* P C R (conventional/real-time) of C S F: Primary application A. cantonensis. Targets parasite D N A. Advantages: High specificity. Limitations: Sensitivity varies with timing.
* AcanR3990 real-time P C R: Primary application A. cantonensis. Targets repetitive genomic D N A in C S F. Advantages: Greater analytical sensitivity than I T S 1 assays. Limitations: Limited clinical validation.
* Broad-range P C R followed by sequencing: Primary application Angiostrongylus species. Targets conserved loci (18S r R N A/I T S-1). Advantages: Detects uncommon species. Limitations: Requires sequencing facilities.
* E L I S A (31-k D a or E/S antigens): Primary application A. cantonensis. Targets anti-Angiostrongylus antibodies. Advantages: Accessible. Limitations: Cannot distinguish active from past infection.
* Immunoblot/E I T B: Primary application A. cantonensis. Targets specific antibodies. Advantages: Improved specificity. Limitations: Serological window period.
* I F A T/I F A: Primary application A. cantonensis. Targets antibodies in serum or C S F. Advantages: Applicable to both fluids. Limitations: Labour-intensive.
* Antigen-capture E L I S A: Primary application A. cantonensis. Targets circulating antigen. Advantages: Indicates active infection. Limitations: Not validated for routine use.
* Immuno-P C R: Primary application A. cantonensis. Targets circulating antigen. Advantages: Very high sensitivity. Limitations: Technically complex.
* AcQuickDx I C T: Primary application A. cantonensis. Targets I g G antibodies. Advantages: Rapid point-of-care. Limitations: Cannot distinguish acute from past infection.
* rAcGal2 I C T: Primary application A. cantonensis. Targets I g G antibodies. Advantages: Promising performance in blood and C S F. Limitations: Requires broader validation.
* AcAgQuickDx I C T: Primary application A. cantonensis. Targets circulating antigen. Advantages: Rapid detection of active infection. Limitations: Limited human validation.
* R P A-L F A: Primary application A. cantonensis. Targets parasite D N A (I T S-1). Advantages: Field-deployable. Limitations: Less sensitive than q P C R.
* m N G S of C S F: Primary application A. cantonensis/atypical neuroangiostrongyliasis. Targets pathogen nucleic acids. Advantages: Broad differential diagnosis. Limitations: Expensive.
* Histopathology of intestinal/mesenteric tissue: Primary application A. costaricensis. Targets adult worms, eggs, and larvae. Advantages: Confirmatory method. Limitations: Invasive biopsy required.
* Tissue P C R: Primary application A. costaricensis. Targets D N A in tissue. Advantages: Species-specific confirmation. Limitations: Limited availability.
* Serology (E L I S A/immunoblot): Primary application A. costaricensis. Targets antibodies. Advantages: Supports diagnosis without tissue. Limitations: Cross-reactivity.
* Abdominal ultrasound/C T: Primary application A. costaricensis. Targets bowel-wall thickening. Advantages: Non-invasive. Limitations: Non-specific findings.
* Peripheral blood eosinophilia: Primary application both species. Targets increased eosinophils. Advantages: Simple supportive test. Limitations: Non-specific.
Treatment
Timely treatment of angiostrongyliasis is essential for immunocompromised patients or those with severe CNS involvement, as delayed intervention can lead to permanent neurological damage or death. All current therapeutic approaches are extrapolated from animal studies and clinical case series, as no randomised trials have definitively established a standard human regimen. in vitro susceptibility testing has confirmed that albendazole, macrocyclic lactones, levamisole, and pyrantel pamoate all possess activity against A. cantonensis larvae; however, no acquired resistance has been reported in clinical settings (Roquini et al. Reference Roquini, Silva, Ferreira, Andricopulo, Wilairatana and De Moraes2022). Corticosteroids form the cornerstone of treatment for neuroangiostrongyliasis. Their benefit derives not from a parasiticidal effect but from suppression of the intense eosinophilic inflammatory response triggered by dying worms in the subarachnoid space. A placebo-controlled trial demonstrated that a 2-week course of prednisolone (60 mg/day) reduced the median duration of headache from 13 to 5 days and significantly reduced the need for repeated therapeutic lumbar punctures (Chotmongkol et al. Reference Chotmongkol, Sawanyawisuth and Thavornpitak2000). Consequently, corticosteroids are recommended for all symptomatic patients (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021):
-
• Mild to moderate disease: prednisolone 60 mg/day orally for at least 2 weeks, with gradual tapering guided by clinical and CSF response (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021; Chotmongkol et al. Reference Chotmongkol, Sawanyawisuth and Thavornpitak2000).
-
• Severe disease (coma, radiculomyelitis): high-dose intravenous methylprednisolone (e.g., 30 mg/kg/day for 5 days) followed by oral prednisolone taper (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021; McAuliffe et al. Reference McAuliffe, Fortin Ensign, Larson, Bavaro, Yetto, Cathey, Mukaigawara, Narita, Ohkusu, Quast and Volk2019).
Anthelmintic therapy, particularly albendazole, has historically remained controversial because of concerns that rapid larval death within the central nervous system could exacerbate inflammation. However, accumulating clinical experience and published evidence increasingly support the use of albendazole, particularly when administered in combination with corticosteroids. A systematic analysis of clinical reports and animal studies found substantial evidence supporting the safety and potential effectiveness of benzimidazole therapy, with albendazole–corticosteroid co-therapy reported as effective in the majority of confirmed clinical cases (Jacob et al. Reference Jacob, Steel, Lin, Berger, Zöeller and Jarvi2022). However, a randomized trial comparing prednisolone plus albendazole with prednisolone alone found no significant difference in headache duration or clinical resolution, highlighting the remaining uncertainty regarding the magnitude of benefit of adjunctive albendazole (Chotmongkol et al. Reference Chotmongkol, Kittimongkolma, Niwattayakul, Intapan and Thavornpitak2009). More recently, an outbreak investigation in Hawai’i involving 6 patients provided additional clinical evidence supporting early albendazole–corticosteroid co-therapy; 5 patients treated within 15 days of infection tolerated the regimen well, with no significant treatment-related adverse events reported (Ansdell et al. Reference Ansdell, Jacob, Gosnell, McMillan, Yates, Lteif, Bicakci, Kaufusi and Kramer2026). Nevertheless, the available evidence remains largely derived from observational studies, case series, and experimental models, and well-designed randomized clinical trials are still needed to establish the optimal timing, dose, and duration of albendazole therapy. When used, the regimen is albendazole 15 mg/kg/day (or mebendazole 10 mg/kg/day) for 14 days, co-administered with corticosteroids from the outset. Albendazole is generally well tolerated; the most notable adverse effect is reversible transaminase elevation (hepatotoxicity), which warrants liver function monitoring (Wang et al. Reference Wang, Lai, Zhu, X-G and Lun2008). Gastrointestinal upset and headache are reported but are difficult to distinguish from the underlying disease. In the published randomized trial, no serious adverse events were attributed to the addition of albendazole, and the safety profile of combination therapy was comparable to corticosteroids alone (Chotmongkol et al. Reference Chotmongkol, Kittimongkolma, Niwattayakul, Intapan and Thavornpitak2009). Therapeutic lumbar puncture can provide rapid relief in patients with raised intracranial pressure and is used alongside corticosteroid therapy (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021; Cowie et al. Reference Cowie, Ansdell, Dunavan and Rollins2022). Despite theoretical concerns, no clinically confirmed anthelmintic resistance in A. cantonensis has been reported (Roquini et al. Reference Roquini, Silva, Ferreira, Andricopulo, Wilairatana and De Moraes2022), and discontinuation of therapy is reserved for significant drug-related adverse effects. Because no drug has been specifically developed for angiostrongyliasis, current practice relies on corticosteroids (adapted from neurocysticercosis protocols) and anthelmintics (repurposed from other helminthiases), underscoring the urgent need for prospective trials to define optimal management (Ansdell et al. Reference Ansdell, Kramer, McMillan, Gosnell, Murphy, Meyer, Blalock, Yates, Lteif, Smith and Melish2021). In contrast to neuroangiostrongyliasis, the management of abdominal angiostrongyliasis caused by A. costaricensis is primarily surgical. Because the disease frequently presents as an acute abdomen mimicking appendicitis or intestinal obstruction, many patients undergo exploratory laparotomy or appendectomy. Resection of the involved bowel segment (usually ileocecal resection) is both diagnostic and therapeutic, as it removes the adult worms and the inflammatory mass (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). Medical therapy with anthelmintics such as albendazole or mebendazole is generally not recommended in abdominal angiostrongyliasis. There is concern that rapid killing of adult worms in the mesenteric vessels may exacerbate local inflammation, increase the risk of thrombosis, or precipitate intestinal perforation (Graeff-Teixeira et al. Reference Graeff-Teixeira, da Silva and Yoshimura2009; Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023). Corticosteroids are sometimes used as adjunctive therapy to reduce the intense granulomatous response, but their benefit is less clearly established than in neuroangiostrongyliasis. Supportive care, including fluid resuscitation, pain management, and antibiotic coverage for secondary peritonitis, is essential in complicated cases. Postoperative recovery is generally favourable, although recurrent episodes have been reported (Rodriguez et al. Reference Rodriguez, Mora, Solano-Barquero, Graeff-Teixeira and Rojas2023; Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021).
Novel treatment developments
Recent research efforts have shifted from purely symptomatic management towards mechanism-based interventions that simultaneously target the parasite and the host inflammatory response. These investigations remain largely preclinical (in murine models) (Lam et al. Reference Lam, Huang, T-R and Peng2024; Roquini et al. Reference Roquini, Silva, Ferreira, Andricopulo, Wilairatana and De Moraes2022), yet they delineate a promising pipeline of adjunctive therapies designed to overcome the limitations of current corticosteroid-centred regimens (Lam et al. Reference Lam, Huang, T-R and Peng2024).
Drug repurposing and new anthelmintic compounds
H1 antihistamines have emerged as potential anthelmintic agents against A. cantonensis larvae, with promethazine and related compounds showing promising activity (Roquini et al. Reference Roquini, Lemes, Kreutz, Spoladore, Amaro, Lopes, Fernandes and de Moraes2024). Structural optimisation of cinnarizine has generated derivatives with improved potency and predicted BBB penetration, supporting their potential for CNS-stage targeting (Lemes et al. Reference Lemes, Siegl-Breno, Silva-Nunes, Lopes, Silva, Motta, Amaro, Roquini, Moraes and Andricopulo2025). Parallel in vivo work on flavonoid compounds identified quercetin as an effective anti-inflammatory agent. Combined albendazole–quercetin therapy in a murine model significantly ameliorated brain pathology, reduced neuroinflammation, and improved neurological deficits compared to monotherapy, acting through inhibition of inflammasome activation and apoptosis (Lam et al. Reference Lam, Huang, T-R and Peng2024). Moreover, cubebin, a lignan isolated from Drimys andina, displayed potent and selective activity against A. cantonensis larvae, proving more efficacious than albendazole in early developmental stages, while remaining safe for mammalian cells (Teixeira et al. Reference Teixeira, Schmidt, Sperlich, Lemes, Amaro, Pérez, Céspedes-Méndez, Villegas, Burgos, de Moraes and Paz2025).
Host-directed therapies
Given the concern that rapid parasite killing with anthelmintics may exacerbate CNS inflammation, combining antiparasitic drugs with modulators of host inflammatory pathways has emerged as a rational strategy. Matrix metalloproteinase (MMP) inhibitors have been at the forefront of this approach. MMP-9 and MMP-12 are critical enzymes involved in BBB disruption and neurovascular matrix degradation during eosinophilic meningitis (Chen and Lai Reference Chen and Lai2024). In a classic study, combined treatment with albendazole and GM6001 (an MMP-9 inhibitor) reduced CSF MMP-9 activity by 89.2%, attenuated inflammatory cell infiltration, and ultimately decreased the number of viable larvae in the brain (Lai et al., Reference Lai, Jiang, Chen, Hsu, Shyu and Lee2005). A more recent investigation showed that doxycycline (which inhibits MMP-12) in combination with albendazole likewise reduced neurological damage in mice (Sofiyatun et al. Reference Sofiyatun, Chen, Chou, Lee, Day, Chiang, Chiu, Chen, Jhan and Wang2025; Wei et al. Reference Wei, Tsai, Chiu and Lai2011). Beyond MMPs, a combined regimen of a PDGFR-β inhibitor (AG1296) and a PI3K inhibitor (LY294002) was shown to suppress MMP-9 activity and the inflammatory cascade, decrease BBB permeability, and protect the neurovascular matrix (Chen and Lai Reference Chen and Lai2024). Additionally, in a model of eosinophilic meningoencephalitis, the CysLT₂ receptor antagonist HAMI3379 diminished cerebral oedema and eosinophil infiltration, shifted the immune response from an M1 to an M2 phenotype, and reduced biomarkers of BBB dysfunction (S100B and claudin-5) (Chen et al. Reference Chen, Lan and Lai2024).
Natural products as therapeutic adjuvants
To minimise reliance on prolonged corticosteroid therapy and its associated adverse effects, several natural products have been evaluated as adjunctive treatments: Schisandrin B, a bioactive compound from Schisandra chinensis, synergised with albendazole in mice to suppress neuroinflammation, improve survival, and shift the immune balance from a Th2-dominant (allergic) response towards a protective Th1-type response (Lam et al. Reference Lam, Liang, S-J and Peng2020). Curcumin, derived from turmeric, demonstrated negligible larvicidal activity when used alone; however, as a complementary agent alongside albendazole, it helped suppress eosinophil counts in the CSF, thereby mitigating the inflammatory milieu of eosinophilic meningitis (Shyu et al. Reference Shyu, Chang, Hsu, Lin, Y-H and Lee2012). Flavonoid compounds have been investigated as adjuncts to anthelmintic therapy in angiostrongyliasis. Quercetin combined with albendazole improved neurological deficits and brain pathology while reducing neuroinflammation via inflammasome inhibition (Lam et al. Reference Lam, Huang, T-R and Peng2024). Tanshinone IIA from Salvia miltiorrhiza attenuated demyelination, promoted remyelination, and shifted the microglial phenotype from M1 to M2 in A. cantonensis-infected mice, while also reducing astrocytic injury in vitro by enhancing cell viability and reducing apoptosis and oxidative stress (Chen and Lai Reference Chen and Lai2024; Feng et al. Reference Feng, Feng, Zheng, Zhou, Jiang, Liu, Xie, Sun and Wu2019).
Immunomodulatory and antibody-based strategies
The deciphering of the host cytokine network has revealed actionable targets. In 2024, a study demonstrated that IL-33 plays a pivotal role in the pathogenesis of A. cantonensis infection by driving elevated total IgG, IgG1, and IgG3 levels. Administration of a monoclonal antibody against IL-33 or its receptor ST2 significantly reduced these antibody titres, highlighting the potential of disrupting the IL-33/ST2 axis to modulate the aberrant immune response (Su et al. Reference Su, Ma, Wu, Wang and Du2024). Furthermore, passive transfer of the monoclonal antibody 12D5 (which targets a 98-kDa adult worm antigen) in infected mice reduced eosinophil infiltration into the brain, mitigated meningitis severity, and markedly improved survival rates, establishing a proof-of-concept for antibody-based immunotherapy in neuroangiostrongyliasis (Li et al. Reference Li, Zhang, Fu, Wu, Chen, Geng, Wang, X-H and Chen2012).
Vaccine development
Vaccine research remains nascent. A recent field trial (2025) evaluated the efficacy of a PP2A vaccine – originally designed for the related species A. costaricensis – against A. cantonensis in wild rats (definitive hosts) in Hawaii. The vaccine failed to induce protective immunity, with no significant differences observed between vaccinated and unvaccinated rats in adult worm counts, organ weights, or cytokine levels (Jarvi et al. Reference Jarvi, Osuna, Pitt, Farias, Shiels, Howe, Jacquier, Shiels, Sugihara, Phan, Gómez Samblás, Friedman, Severino, Amano, Allison, Luiz and Holtquist2025). This outcome emphasizes the imperative to develop dedicated vaccines based on A. cantonensis-specific antigens, such as those from the 31-kDa protein family.
RNA-based therapies
Exploiting regulatory RNA pathways has opened a novel therapeutic frontier. Delivery of microRNA-200s to target phosphatase and tensin homolog (PTEN) in a mouse model reduced demyelination lesions in the CNS and improved neurobiological functions (Xiong et al. Reference Xiong, Ma, Li, Niu, Yang, Wu, Wang, Zhang and Chen2026). In a complementary approach, adeno-associated virus (AAV) vectors expressing tough decoy (TuD) RNA inhibitors were used to achieve sustained inhibition of mmu-miR-101b-3p. This strategy attenuated pathological damage induced by A. cantonensis by disrupting the expression of the parasite’s superoxide dismutase 3 enzyme, thereby enhancing host oxidative defence mechanisms against the nematode (Yuan et al. Reference Yuan, Luo, Xu, Zeng and Wu2019). In summary, contemporary research has decisively moved beyond empirical supportive care. The convergence of novel anthelmintics, host-directed anti-inflammatory agents, natural adjuvant compounds, and molecular RNA-based interventions holds promise for developing safer and more efficacious multi-target therapeutic protocols for this globally emerging zoonosis. However, all these findings are confined to preclinical models and require rigorous validation in human clinical trials. The principal therapeutic strategies for neuroangiostrongyliasis and abdominal angiostrongyliasis, including established, adjunctive, surgical, and experimental approaches, are summarized in Table 2.
Therapeutic strategies for human angiostrongyliasis and their primary application to Angiostrongylus species
Table 2. Long description
The table consists of 14 rows of treatment data across five columns.
1. Oral prednisolone for A. cantonensis: Suppresses eosinophilic C N S inflammation. It is a cornerstone of symptomatic treatment but has no direct antiparasitic activity.
2. Intravenous methylprednisolone for severe A. cantonensis: Potent suppression of severe C N S inflammation. Useful in coma or radiculomyelitis but usually requires hospitalization.
3. Therapeutic lumbar puncture for A. cantonensis: Reduces intracranial pressure via C S F drainage. Provides rapid relief but is invasive.
4. Albendazole plus corticosteroids for A. cantonensis: Anthelmintic activity plus inflammatory suppression. Increasing clinical support but optimal timing is undefined.
5. Mebendazole plus corticosteroids for A. cantonensis: Alternative benzimidazole regimen with limited human evidence.
6. Supportive therapy for A. cantonensis: Analgesia and hydration. Essential but does not eliminate the parasite.
7. Surgical resection for A. costaricensis: Removal of inflamed bowel. Diagnostic and therapeutic for obstructions but invasive.
8. Exploratory laparotomy/appendectomy for A. costaricensis: Management of acute abdomen. May establish diagnosis when mimicking appendicitis.
9. Supportive care for A. costaricensis abdominal disease: Fluid replacement and analgesia. Does not eliminate adult worms.
10. Corticosteroids as adjunctive therapy for A. costaricensis: Potential suppression of inflammatory response. Role is not established as standard therapy.
11. Anthelmintic therapy for A. costaricensis: Parasite killing. Not routinely recommended as parasite death may aggravate inflammation.
12. Experimental host-directed therapies (M M P, P I 3 K / P D G F R-beta, or Cys L T sub 2 R inhibitors) for A. cantonensis: Reduction of neuroinflammation and blood-brain barrier disruption. Preclinical evidence only.
13. Experimental natural-product adjuvants (quercetin, schisandrin B, curcumin) for A. cantonensis: Modulation of inflammation. Preclinical evidence only.
14. Experimental immunomodulatory/antibody-based approaches for A. cantonensis: Modulation of host immune responses. No established human indication.
Future directions
Research on human angiostrongyliasis has accelerated over the past decade, particularly in relation to transmission dynamics, molecular diagnosis, and experimental therapeutics. However, substantial gaps remain as the disease expands beyond its historical geographic boundaries. The geographic range of A. cantonensis continues to widen, with autochthonous transmission documented in continental Europe and newly reported in South America, including Argentina (Galán-Puchades et al. Reference Galán-Puchades, Gómez-Samblás, Osuna, Sáez-Durán, Bueno-Marí and Fuentes2023; Hancke et al. Reference Hancke, Guzman, Tripodi, Muschetto and Suárez2024). Recent evidence from eastern Australia further indicates that rainfall and temperature variability can influence transmission intensity, highlighting the importance of climate-responsive surveillance in emerging endemic areas (Rivory et al. Reference Rivory, Lee, Ward and Šlapeta2025). Sentinel hosts may also support environmental surveillance; for example, endemic lizards have been proposed as useful indicators of A. cantonensis distribution in island ecosystems (Anettová et al. Reference Anettová, Baláž, Coufal, Horsák, Izquierdo-Rodriguez, Šipková, Foronda and Modrý2024). Climate-driven ecological niche modelling provides an additional framework for anticipating future transmission. Recent modelling of Pomacea canaliculata under different climate scenarios predicted geographic shifts in suitable habitat and identified priority regions for surveillance and intervention (Li et al. Reference Li, Wang, Chen, Shan, Wang, Wang, Zhang, Liu and Zhou2026). Future models should incorporate multiple gastropod species and geographic settings to improve prediction of emergence risk and guide climate-adaptive public health strategies. Diagnosis remains a major research priority, particularly in atypical cases in which peripheral or CSF eosinophilia may be absent. Metagenomic next-generation sequencing (mNGS) has demonstrated potential for detecting A. cantonensis when conventional diagnostic approaches are inconclusive, although its high cost and infrastructure requirements limit widespread implementation. A context-specific diagnostic workflow combining mNGS with inexpensive, field-deployable approaches such as LAMP and rapid antigen tests may therefore be more appropriate for resource-limited settings (Rattanapitoon et al. Reference Rattanapitoon, Thanchonnang, Arunsarn and Rattanapitoon2025; Tang et al. Reference Tang, Wu, Yang, Wang, Jin, Xie, Zhang, Chen and Li2025). Future diagnostic research should also focus on broader validation of rapid point-of-care assays and development of platforms capable of distinguishing active infection from previous exposure. Therapeutic research should prioritize evidence-based evaluation of adjunctive and host-directed interventions. Although corticosteroids remain the cornerstone of neuroangiostrongyliasis management, the optimal role of anthelmintic therapy remains incompletely defined. Preclinical studies of albendazole and host-directed agents, including anti-inflammatory and blood–brain barrier-targeting compounds, provide promising leads but require validation in well-designed clinical trials. Future studies should establish the optimal timing, dose, and duration of combination therapy and identify biomarkers that can predict treatment response. Vaccine development also remains at a preclinical stage. The failure of a PP2A vaccine originally developed for A. costaricensis to protect rats against A. cantonensis highlights the need for species-specific vaccine targets and more effective strategies for cross-species or multivalent protection (Jarvi et al. Reference Jarvi, Osuna, Pitt, Farias, Shiels, Howe, Jacquier, Shiels, Sugihara, Phan, Gómez Samblás, Friedman, Severino, Amano, Allison, Luiz and Holtquist2025). Future vaccine research should focus on immunogenic antigens expressed during relevant larval and adult stages and evaluate their protective efficacy in appropriate animal models. In the absence of licensed vaccines and fully validated treatment strategies, prevention remains dependent on interruption of foodborne transmission. Public health interventions should emphasize avoidance of raw or undercooked gastropods and paratenic hosts, thorough washing of fresh vegetables, and rodent control (Rojas et al. Reference Rojas, Maldonado-Junior, Mora, Morassutti, Rodriguez, Solano-Barquero, Tijerino, Vargas and Graeff-Teixeira2021). Educational programmes should be strengthened in endemic and newly affected regions, while climate-resilient transmission hotspots should be prioritised for integrated surveillance and targeted intervention (Li et al. Reference Li, Wang, Chen, Shan, Wang, Wang, Zhang, Liu and Zhou2026; Wang et al. Reference Wang, Wu, Wei, Owen and Lun2012). Overall, future progress will require coordinated One Health strategies integrating environmental surveillance, accessible diagnostics, evidence-based treatment, food-safety education, and ecological management.
Financial support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
The author(s) declare none.
