Angiostrongylus Cantonensis Research Articles

Angiostrongylus cantonensis Meningoencephalitis in Three Pediatric Patients in Florida, USA.

Eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis has been reported in several southern U.S. states and Hawai'i. We present the first locally acquired human cases of A. cantonensis meningoencephalitis in three children in Florida, occurring between June 2021 and January 2022. Clinicians should be attuned to this possible diagnosis in this region.

Identifying the function of novel cross-species microRNAs from the excretory-secretory products of Angiostrongylus cantonensis fifth-stage larvae

Identifying the function of novel cross-species microRNAs from the excretory-secretory products of Angiostrongylus cantonensis fifth-stage larvae

A Scoping Review of Angiostrongyliasis and Other Diseases Associated with Terrestrial Mollusks, Including Lissachatina fulica: An Overview of Case Reports and Series.

Terrestrial mollusks, including the invasive giant African snail (Lissachatina fulica), pose significant public health risks due to their role as carriers of various pathogens, such as Angiostrongylus cantonensis and Angiostrongylus costaricensis. This scoping review aims to provide a comprehensive evaluation of diseases associated with Lissachatina fulica and other terrestrial mollusks, with a particular focus on the prevention, diagnosis, and treatment of these conditions. Following the Joanna Briggs Institute guidelines and the PRISMA-ScR framework, we conducted a systematic search and filtered results, identifying 27 relevant case reports and series for analysis. Our findings reveal that ingesting raw or undercooked snails is the most hazardous exposure route, with a 75% mortality rate in affected adults, particularly in regions where snail consumption is culturally significant, such as France. A. cantonensis is the primary cause of eosinophilic meningitis, while A. costaricensis leads to abdominal angiostrongyliasis. The review also highlights the widespread impact of L. fulica in countries like France, the United States, Brazil, and Colombia, emphasizing the global nature of the threat. Children show consistent vulnerability across all exposure types, underscoring the need for targeted preventive strategies. This review underscores the urgent need for public health interventions, particularly educational campaigns to inform communities about the dangers of L. fulica. Additionally, it highlights the importance of enhancing diagnostic methods and expanding surveillance to better manage the risks associated with these invasive snails. The findings provide valuable insights for the scientific community and recommend a multidisciplinary approach to effectively mitigate the public health risks posed by L. fulica across diverse regions.

Co-introduction into a delicate island ecosystem: metastrongyloid nematodes (superfamily Metastrongyloidea) of veterinary and medical importance circulating in aquatic and terrestrial environments of Tenerife (Canary Islands).

Metastrongyloid nematodes typically reside as adults in the cardiopulmonary systems of their mammalian definitive hosts, potentially causing severe diseases. Of particular concern are Angiostrongylus cantonensis and A. costaricensis, which can cause eosinophilic meningitis and abdominal angiostrongyliasis, respectively, in their accidental human hosts. Several metastrongyloid species of medical and veterinary importance have been documented in the Canary Islands. However, the gastropod species acting as intermediate hosts for some of these nematodes in the archipelago remained unknown. This study aimed to investigate the occurrence of metastrongyloid nematodes in terrestrial and aquatic gastropods, including both endemic and non-native species, on Tenerife. Foot samples from terrestrial and aquatic gastropods were analyzed using a multiplex PCR targeting the Internal Transcribed Spacer 1 (ITS1), allowing the specific detection of A. cantonensis, A. vasorum, Aelurostrongylus abstrusus, Crenosoma striatum, Troglostrongylus brevior, and Crenosoma vulpis. Five metastrongyloid species, namely C. striatum, A. cantonensis, Ae. abstrusus, A. vasorum, and an unidentified metastrongyloid, were identified within both non-native and endemic terrestrial gastropods. In the aquatic snail Physella acuta, only A. cantonensis and C. striatum were detected. This study confirms the introduction of various metastrongyloids associated with non-native mammalian fauna and provides new data on the occurrence of these nematodes in non-native and endemic gastropod species, including their presence in aquatic environments on the Canary Islands.

Low potential of fish as a source of infection with Angiostrongylus cantonensis

Abstract Objectives Fish are hypothesized to act as paratenic hosts for the zoonotic nematode Angiostrongylus cantonensis, cause of human eosinophilic meningitis. There is a lack of data confirming the relevance of fish in A. cantonensis life cycle and their contribution to human infection. Materials and methods We conducted a series of experiments to investigate survival and infectivity of A. cantonensis larvae in Clarias gariepinus (catfish; n=30) and Oreochromis niloticus (tilapia; n=24). Each fish was inoculated with 10,000 third-stage larvae (L3). Larval survival was assessed through artificial digestion of fish tissues one, two, and three weeks post-infection. To investigate early stages of infection, four catfish were inoculated with 10,000 L3 each and sacrificed 3 days post-infection. qPCR and histopathological examinations were performed to evaluate larval distribution and tissue reactions. Two infected catfish, sacrificed one week post-infection, were used to feed Wistar rats. Results After 45 days, the rats were not shedding L1, indicating the absence of infection. One week post-infection, dead larvae were present in digested tissues of both fish species, and the same was observed two and three weeks after exposure. qPCR analysis revealed that intestine was the most heavily infected organ. Histopathology identified dead larvae within granulomas in intestines and liver. Early-stage infection experiment showed that fish sacrificed three days post-inoculation contained viable L3 which were infective to Wistar rats. Conclusions While A. cantonensis L3 can survive and remain infective in fish for a short period, they typically die within first few days post-infection. This suggests that fish may not be significant long-term paratenic hosts for A. cantonensis but may play a temporary role in its transmission to mammals (including humans) and birds. These results are consistent with previous studies on freshwater shrimps and highlight the importance of understanding aquatic host interactions in the epidemiology of this zoonotic food-borne pathogen.

Reaching new lands: Updating the distribution of Angiostrongylus cantonensis in South America with the first record in Argentina.

Angiostrongylus cantonensis, commonly known as the rat lungworm, is a metastrongyloid nematode found primarily not only in tropical and subtropical regions but also in temperate areas and considered the leading cause of eosinophilic meningitis in humans. Synanthropic rodents such as Rattus norvegicus and Rattus rattus are the most frequent definitive hosts of this parasite. The presence of this parasite was detected in the pulmonary arteries of three specimens of R. norvegicus in the city of Buenos Aires representing the species' southernmost known record in natural hosts. Species confirmation was achieved through partial sequences of 18S and COI genes. By comparing the COI gene sequences with those available in GenBank through the construction of a haplotype network, we obtained that the analysed specimen presents high similarity with those reported in Japan and Southeast Asia. All infected rats were captured in an area surrounding a port with significant import and export activity, suggesting that A. cantonensis may have been introduced through commercial ships. Specifically, the parasite was detected in a neighbourhood with vulnerable socio-economic conditions and in a nature reserve, which exhibit biotic and abiotic characteristics conducive to sustaining high-density rat populations, scattered waste, areas of spontaneous vegetation, debris accumulation and flooded areas or lagoons offering suitable habitats for intermediate hosts such as snails. Thus, the close proximity of the port to these sites creates a favourable ecological context for the establishment of A. cantonensis. This study shows the need to conduct research to detect A. cantonensis in non-endemic areas but with the characteristics that promote its arrival and development of its life cycle in order to implement control measures to prevent expansion of this parasite and its transmission to humans and other animals.

Severe Neuropathic Back Pain as the Initial Presentation in Angiostrongylus cantonensis Infection: The Role of ICU Management in Overcoming Diagnostic and Analgosedation Challenges

Introduction: Angiostrongylus cantonensis is a parasitic nematode that typically inhabits the pulmonary arteries of rats but can also reside in the central nervous systems of rats and mollusks. Humans can become infected with A. cantonensis by eating infected hosts or consuming contaminated food, especially if it is raw or undercooked. This infection can lead to various neurological symptoms, including neuropathic pain, which is often an early indication of the condition. In this report, we present a case in which the patient experienced neuropathic pain as the initial clinical manifestation of A. cantonensis infection. Case Presentation: We present a rare case of a 27-year-old female who required intensive care unit (ICU) monitoring due to heavy sedation after receiving high doses of sedative-analgesics for back pain. The patient reported experiencing severe, slow-progressing low back pain radiating to her arms and legs. The pain was described as sharp, tingling, and numbing, severely limiting her movements. To manage the pain, a combination of morphine, intermittent fentanyl, ketamine, dexmedetomidine, duloxetine, and pregabalin was administered. Consequently, the patient had to be intubated due to the effects of the analgesics. During the first two weeks in the ICU, diagnosis proved challenging as the MRI was normal and the initial lumbar puncture revealed only an eosinophilic infection. However, during a follow-up lumbar puncture, multiple parasites were discovered in the cerebrospinal fluid, which were identified as A. cantonensis. The patient remains on a ventilator as the infection has affected the spinal nerve roots, cord, meninges, and brain. We explore the crucial role of ICU care in providing both supportive and definitive treatment for this patient. Conclusions: This report underscores the critical role of the ICU in providing care for a patient with a progressively deteriorating condition without an initial definitive diagnosis. The ICU's ability to deliver optimal pain relief and sedation, advanced monitoring, and prompt therapy for deteriorating symptoms was of utmost significance. Furthermore, the multidisciplinary team in the ICU was instrumental in managing the continuum of care for the patient.

Nematodes of concern to public and animal health associated with the invasive snail Achatina fulica, in Sergipe, Northeastern Brazil

The giant African land snail Achatina fulica is known to be the intermediate host of a number of nematode species that are prejudicial to human and veterinary health, being also an agricultural and urban pest. The present study investigated the presence of nematodes in A. fulica and other terrestrial mollusks in 24 municipalities of Sergipe State, northeastern of Brazil, in the dry and rainy seasons. In 2019 and 2020, the specimens were collected in standard 20 m × 10 m plots (10 min/01 collector), while in 2021, they were collected by convenience sampling. The nematode species were identified based on sequencing of the mitochondrial Cytochrome C Oxidase Subunit I (COI) gene and the ribosomal nuclear Internal Transcribed Spacer (ITS 2). Specimens of A. fulica infected with Angiostrongylus cantonensis, a nematode that causes eosinophilic meningitis (EM) in humans and animals, were collected in four municipalities. Two nematodes of veterinary importance were also identified, Aelurostrongylus abstrusus and Cruzia tentaculata in seven municipalities. This is the first record of Cruzia tentaculata in Sergipe. Free-living nematodes were also found in 18 municipalities. One of these species – Caenorhabditis briggsae – was identified in the municipality of Itabaiana. Specimens of other mollusks species were also collected. Only one of these mollusks, C. fasciata from Japaratuba, was found infected with free-living nematodes. A. fulica showed greater positivity for nematodes in the dry season, especially in the regions of Lower São Francisco River, Greater Aracaju and South Central Sergipe. The probability of infection increased when mollusks were larger and more recurrent in plots. Given that A. cantonensis is the etiological agent of EM and was found associated to A. fulica in four municipalities, it will be important to implement programs of continuous monitoring of the mollusk's fauna, combined with educational programs that provide information necessary to control A. fulica.

Diagnosis of human angiostrongyliasis in a case of hydrocephalus using next-generation sequencing: a case report and literature review

BackgroundAngiostrongyliasis cantonensis is a severe yet rare parasitic infection caused by the larvae of Angiostrongylus cantonensis. The primary characteristic feature of this foodborne illness in humans is eosinophilic meningitis. Recently, there has been a gradual increase in reported cases globally. Due to the lack of typical clinical symptoms, signs, and specific laboratory tests, early diagnosis of this disease poses significant challenges. Failure to diagnose and treat this condition promptly can result in fatalities.MethodsWe present the case of a 13-year-old male patient who initially presented with fever and headache. The patient was preliminarily diagnosed with bacterial meningitis and received treatment with antibacterial drugs. However, the patient’s condition worsened, and he developed progressive consciousness disturbances. Eventually, metagenomic next-generation sequencing (mNGS) testing of cerebrospinal fluid samples indicated Angiostrongylus cantonensis infection. Following treatment with albendazole and prednisone, the patient made a full recovery. We include this case report as part of a literature review to emphasize the potential applications of mNGS in the early diagnosis of Angiostrongyliasis cantonensis.ConclusionmNGS technology plays a crucial role in the diagnosis of angiostrongyliasis cantonensis. As this technology continues to evolve and be applied, we believe it will play an increasingly important role in diagnosing, treating, and monitoring angiostrongyliasis cantonensis.

Benzaldehyde stimulates autophagy via the sonic hedgehog signaling pathway in mouse brain astrocytes after treatment with Angiostrongylus cantonensis excretory-secretory products

Autophagy is a vital cellular process responsible for digesting various cytoplasmic organelles. This process plays a crucial role in maintaining cell survival and homeostasis, especially under conditions that cause nutrient deficiency, cellular damage, and oxidative stress. Neuroangiostrongyliasis is an infection caused by the parasitic nematode Angiostrongylus cantonensis and is considered as an emerging disease in many parts of the world. However, effective therapeutic strategies for neuroangiostrongyliasis still need to be further developed. In this study, we investigated the effects of benzaldehyde treatment on autophagy and sonic hedgehog (Shh) signaling in A. cantonensis-infected mice and its mechanisms. First, we found autophagosome generation in the central nervous system after A. cantonensis infection. Next, benzaldehyde combined with albendazole treatment reduced eosinophilic meningitis and upregulated the expression of Shh signaling- and autophagy-related molecules in A. cantonensis-infected mouse brains. In vitro experiments demonstrated that benzaldehyde could induce autophagy via the Shh signaling pathway in A. cantonensis excretory-secretory products (ESPs)-treated mouse astrocytes. Finally, benzaldehyde treatment also decreased lipid droplet accumulation and increased cholesterol production by activating the Shh pathway after ESPs treatment. In conclusion, these findings suggested that benzaldehyde treatment could alleviate brain damage by stimulating autophagy generation through the Shh signaling pathway.

Seek, and you will find: Cryptic diversity of the cardiopulmonary nematode Angiostrongylus vasorum in the Americas

Angiostrongylus vasorum is a metastrongylid parasite infecting wild canids and domestic dogs. Its patchy distribution, high pathogenicity and taxonomical classification makes the evolutionary history of A. vasorum intriguing and important to study. First larval stages of A. vasorum were recovered from feces of two grey foxes, Urocyon cinereoargenteus, from Costa Rica. Sequencing and phylogenetic and haplotypic analyses of the ITS2, 18S and cytochrome oxidase subunit 1 (cox1) fragments were performed. Then p- and Nei´s genetic distance, nucleotide substitution rates and species delimitation analyses were conducted with cox1 data of the specimens collected herein and other Angiostrongylus spp. Cophylogenetic congruence and coevolutionary events of Angiostrongylus spp. and their hosts were evaluated using patristic and phenetic distances and maximum parsimony reconciliations. Specimens from Costa Rica clustered in a separate branch from European and Brazilian A. vasorum sequences in the phylogenetic and haplotype network analyses using the ITS2 and cox1 data. In addition, cox1 p-distance of the sequences derived from Costa Rica were up to 8.6 % different to the ones from Europe and Brazil, a finding mirrored in Nei´s genetic distance PCoA. Species delimitation analysis supported a separate group with the sequences from Costa Rica, suggesting that these worms may represent cryptic variants of A. vasorum, a new undescribed taxon or Angiocaulus raillieti, a synonym species of A. vasorum described in Brazil. Moreover, nucleotide substitution rates in A. vasorum were up to six times higher than in the congener Angiostrongylus cantonensis. This finding and the long time elapsed since the last common ancestor between both species may explain the larger diversity in A. vasorum. Finally, cophylogenetic congruence was observed between Angiostrongylus spp. and their hosts, with cospeciation events occurring at deeper taxonomic branching of host order. Altogether, our data suggest that the diversity of the genus Angiostrongylus is larger than expected, since additional species may be circulating in wild canids from the Americas.

Resposta reprodutiva de Bulimulus tenuissimus (Mollusca) como hospedeiro intermediário de Angiostrongylus cantonensis (Nematoda)

The snail Bulimulus tenuissimus is a terrestrial gastropod widely distributed in the Americas, Asia, Africa and some countries of other continents. It typically occurs in the same areas as Angiostrongylus cantonensis, which needs a mollusk as intermediate host. In spite of this, the literature is scant about the relationship of these organisms. Specimens of B. tenuissimus were experimentally infected with L1 larvae of A. cantonensis. Weekly, until the third week post exposure, the reproductive parameters were analyzed and snails were dissected for collection of hemolymph, along with the albumen gland and tissues for histological analysis. The total number of eggs laid, total number of newly hatched snails and number of newly hatched snails/eggs laid were higher in the infected snails, but the differences observed were not significant. The galactogen content in the albumen gland was significantly reduced from the second week post exposure onward. Also, in spite of presence of larvae in the gonadal region of the snail with granuloma-like structures and some histological changes, gametogenesis occurred regularly in the infected hosts. The results are worrisome, since they showed that B. tenuissimus is an intermediate host to A. cantonensis which supports infection without changes in its reproductive biology and activity. The present study sheds more light on a snail that is a newly recorded experimental and natural intermediate host of A. cantonensis, which is widely distributed and occurs in areas were neural angiostrongyliasis has been recorded. Therefore, this snail can act in the nature as an important agent for dispersion of neural angiostrongyliasis, posing a serious problem to human and animal public health.

A new diagnostic technique for identifying Angiostrongylus spp. larvae in intermediate snail species by examining the buccal cavity

BackgroundAngiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis.MethodsIn this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure.ResultsWe found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods.ConclusionsThis study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.Graphical

Antihistamines H1 as Potential Anthelmintic Agents against the Zoonotic Parasite Angiostrongylus cantonensis.

Infections caused by parasitic helminths pose significant health concerns for both humans and animals. The limited efficacy of existing drugs underscores the urgent need for novel anthelmintic agents. Given the reported potential of antihistamines against various parasites, including worms, this study conducted a screening of clinically available antihistamines against Angiostrongylus cantonensis-a nematode with widespread implications for vertebrate hosts, including humans. Twenty-one anti-H1 antihistamines were screened against first-stage larvae (L1) of A. cantonensis obtained from the feces of infected rats. Standard anthelmintic drugs ivermectin and albendazole were employed for comparative analysis. The findings revealed four active compounds (promethazine, cinnarizine, desloratadine, and rupatadine), with promethazine demonstrating the highest potency (EC50 = 31.6 μM). Additionally, morphological analysis showed that antihistamines induced significant changes in larvae. To understand the mechanism of action, antimuscarinic activities were reported based on average pK i values for human muscarinic receptor (mAChR) subtypes of the evaluated compounds. Furthermore, an analysis of the physicochemical and pharmacodynamic properties of antihistamines revealed that their anthelmintic activity does not correlate with their activity at H1 receptors. This study marks the first documentation of antihistamines' activity against A. cantonensis, offering a valuable contribution to the quest for novel agents effective against zoonotic helminths.

Detection of rat lungworm (Angiostrongylus cantonensis) infection by real-time PCR from the peripheral blood of animals: a preliminary study

Rat lungworm disease or neuroangiostrongyliasis is a cerebral parasitic infection that affects humans and animals alike. Its clinical signs and symptoms can range from mild self-resolving to serious life-threatening conditions. Studies suggest therapeutic interventions during the early stages of infection to be more effective than in later stages. However, early diagnosis of infection is usually problematic without the knowledge of exposure and/or detection of the parasite’s DNA or antibody against the parasite in the cerebrospinal fluid. This requires a lumbar puncture, which is an invasive procedure that generally requires hospitalization. This study evaluates an affordable and less invasive alternative to detect parasitic DNA by PCR from the peripheral blood of potentially infected animals. Blood samples from 58 animals (55 dogs and 3 cats) with clinical suspicion of infection were submitted to our lab between February 2019 and August 2022 by local, licensed veterinarians. DNA was extracted from whole blood, plasma, serum, and/or packed cells using the Qiagen DNeasy Blood & Tissue Kit as per the manufacturer’s protocol. All 58 animals were tested by real-time PCR using the AcanITS1 assay and 32 of these animals (31dogs; 1 cat) were also tested using the AcanR3990 assay. The PCR results for both assays were classified into strongly positive > positive > weakly positive > negative, and equivocal for ambiguous results, based on the strength of the signal. The percent infection detected using the AcanITS1 and AcanR3990 assays was 12.72% (7/55) and 20.68% (6/29), respectively. The overall percent infection detected was 34.37% (11/32), with only two animals testing positive by both assays. The three cats involved in this study tested negative by both assays. These results are promising and warrant further investigations to increase sensitivity including variables that might affect detection in the blood, such as parasite load, and laboratory methodologies.

Inflammatory and immunopathological differences in brains of permissive and non-permissive hosts with Angiostrongylus cantonensis infection can be identified using 18F/FDG/PET-imaging.

Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. 18F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using in vivo 18F-FDG PET imaging. Non-permissive host ICR mice and permissive host SD rats were infected with A. cantonensis, and the effects of the resulting inflammation on 18F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of 18F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-γ and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that 18F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain. An in vivo 18F-FDG/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of A. cantonensis-infected mice and rats.

Exploration of the Molecular Mechanism by Which Caveolin-1 Regulates Changes in Blood-Brain Barrier Permeability Leading to Eosinophilic Meningoencephalitis.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Screening the Efficacy and Safety of Molluscicides from Three Leaf Extracts of Chimonanthus against the Invasive Apple Snail, Pomacea canaliculata.

Pomacea canaliculata, the invasive snail, is a host of the parasitic nematode Angiostrongylus cantonensis, which has adverse effects on the agriculture system and human health. This work evaluated the molluscicidal activity of petroleum ether extracts (PEEs) from three species of Chimonanthus against the snail P. canaliculate. Pcp (PEE of C. praecox) showed the most effective molluscicide activity. Sixty-one compounds were identified by GC-MS and the main components were terpenoids and fatty acids. The half-lethal concentration (LC50) of Pcp at 24 h (0.27 mg/mL) and 48 h (0.19 mg/mL) was used to evaluate the biochemical alterations in snail tissue. These sublethal concentrations caused the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity to increase, while acetylcholinesterase (AChE) activity decreased. Also, under LC50 treatment, several histological changes were observed in the hepatopancreas and foot of the snail compared with the control group. Moreover, the toxic test in rice demonstrated that Pcp has low toxicity. These results suggest that Pcp could be developed as an effective molluscicide for P. canaliculata control.

Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection

Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2–3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.

Rat lungworm, Cryptosporidium and other zoonotic pathogens of Rattus rattus and native wildlife on Sydney's Northern beaches

ABSTRACT Urbanisation is disrupting natural habitats and potentially causing spillover of zoonotic diseases from animals common in highly populated areas to natural environments and native wildlife. The black rat (Rattus rattus) is a common commensal species abundant in urban areas and nearby bushland in Australia and globally. It can be a major reservoir of pathogens and vectors for diseases that affect humans, pets, and wildlife. We examined pathogen prevalence in black rats and native wildlife in peri-urban northern Sydney. We trapped rats and native wildlife at eight 1-ha bushland sites and sampled for a range of internal pathogens from necropsied individuals (n=85 rats) and animal/trap swabs (n=54 native individuals). We detected a high prevalence of rat lungworm (Angiostrongylus spp.) in black rats (67%) as well as native wildlife including long-nosed bandicoots (Perameles nasuta; 43%; previously undetected) and bush rats (R. fuscipes; 33%). Incidence of detection tended to be more frequent where rat activity was greatest. Non-zoonotic Cryptosporidium spp. was also recorded in 17% of black rats and Salmonella spp. in 21% of bandicoots. Our findings suggest black rats may be facilitating spill-over of disease into native wildlife. The detected prevalence of Angiostrongylus spp. suggests an increasing occurrence in this natural system. These data provide valuable insight for disease management highlighting important reservoirs of disease which could be targeted to reduce disease burden in humans, pets, and wildlife.