Cerebral Angiostrongyliasis Research Articles

Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis

BackgroundWe investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment. Materials and methodsC57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis. ResultsIn this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system. ConclusionsCombination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.

Protective effect of benzaldehyde combined with albendazole against brain injury induced by Angiostrongylus cantonensis infection in mice

Angiostrongylus cantonensis, which is also known as rat lungworm, is an important food-borne zoonotic parasite that causes severe neuropathological damage and symptoms, including eosinophilic meningitis and eosinophilic meningoencephalitis, in humans. At present, the therapeutic strategy for cerebral angiostrongyliasis remains controversial. Benzaldehyde, an important bioactive constituent of Gastrodia elata (Tianma) reduces oxidative stress by inhibiting ROS production. This study aimed to evaluate the therapeutic effect of benzaldehyde in combination with albendazole on angiostrongyliasis in animal models. First, the data from body weight monitoring and behavioural analyses demonstrated that benzaldehyde improve body weight and cognitive function changes after A. cantonensis infection. Next, blood‒brain barrier breakdown and pathological changes were reduced after benzaldehyde and albendazole treatment in A. cantonensis-infected BALB/c mice. Subsequently, we established four RNA-seq datasets from different treatment mouse brains, including the normal, infection, infection+albendazole, and infection+albendazole+3-HBA groups. Ultimately, we found that benzaldehyde regulates cell apoptosis, oxidative stress, and sonic hedgehog signalling in A. cantonensis-infected mouse brains. This study evaluated the therapeutic effect of benzaldehyde on angiostrongyliasis and provided a potential therapeutic strategy for human angiostrongyliasis in the clinic. Moreover, we elucidated the molecular mechanism of benzaldehyde in A. cantonensis-infected mouse brains.

The invasive giant African land snail, Achatina fulica (Gastropoda: Pulmonata): global geographical distribution of this species as host of nematodes of medical and veterinary importance.

The giant African land snail, Achatina fulica, is an important invasive species in many countries, where it causes losses in biodiversity and agriculture, as well as impacting the health of both humans and animals, as the intermediate host of medically important nematodes. The present study is based on a comprehensive review of the literature on the nematodes that have been found in association with A. fulica, worldwide. We searched a number of different databases and used the findings to investigate the methods used to extract and identify the nematodes, their larval stages, and environment and collecting procedures of the infected molluscs. Between 1965 and 2021, 11 nematode species were recorded in association with A. fulica in 21 countries. Most of the studies recorded associations between A. fulica and Angiostrongylus cantonensis, which causes cerebral angiostrongyliasis in humans and Aelurostrongylus abstrusus, which provokes pneumonia in felines. The nematodes were extracted primarily by artificial digestion with hydrochloric acid or pepsin, and identified based on their morphology or through experimental infection to obtain the adult. In most cases, the nematodes were at larval stage L3, and the infected A. fulica were collected from anthropogenic environments. The results demonstrate the importance of A. fulica as a host of nematodes of medical and veterinary importance, as well the contribution of anthropogenic environments to the occurrence of the parasites, and give information about the different methods used to collect and identify the nematodes found associated with this species.

Terrestrial Slugs in Neotropical Agroecosystems

Slugs can be important agricultural pests in tropical regions. They are also intermediate hosts of parasitic nematodes, such asAngiostrongylus costaricensisandA. cantonensis, which can cause abdominal and cerebral angiostrongyliasis in humans. Management of slugs in conventional agriculture has relied heavily in the use of pellets containing metaldehyde. In this article, we review cases of slug problems and their management in neotropical agroecosystems.

Terrestrial slugs in neotropical agroecosystems.

Slugs can be important agricultural pests in tropical regions. They are also intermediate hosts of parasitic nematodes, such as Angiostrongylus costaricensis and A. cantonensis, which can cause abdominal and cerebral angiostrongyliasis in humans. Management of slugs in conventional agriculture has relied heavily in the use of pellets containing metaldehyde. In this article, we review cases of slug problems and their management in neotropical agroecosystems.

Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with Angiostrongylus cantonensis: Histopathological and RNA-seq Analyses.

Administration of albendazole alone was not very suitable for the treatment of cerebral angiostrongyliasis. This study was designed to evaluate the effects of the co-therapy of this drug and dexamethasone in Th-1 and Th-2 dominant mice infected with Angiostrongylus cantonensis. Each of BALB/c and C57BL/6 mice infected with 50 A. cantonensis third-stage larvae were administered albendazole (10 mg/kg/day) alone, dexamethasone (0.5 mg/kg/day) alone, or co-therapy of the two drugs from day 7 or 14 post-infection for 7 or 14 days. After sacrifice, coronal slices were prepared from five brain regions and stained with hematoxylin and eosin. Eight pathological changes were employed to determine the therapeutic effectiveness using a scoring system. RNA-seq analysis was performed to confirm the histopathological findings. The infected BALB/c and C57BL/6 mice had similar patterns in the pathological changes. Meningitis, hemorrhage, size of worms, and encephalitis in the cerebral parenchyma were slighter in the mice treated with co-therapy than the remaining groups. Mice treated from day 14 had more severe changes than those from day 7. The histopathological findings were found to be consistent to immune responses determined by RNA-seq analysis. Co-therapy was determined to reduce pathological changes after administration to mice infected with A. cantonensis.

De novo transcriptome reveals blood coagulation/antithrombin factors and infection mechanisms in Angiostrongylus cantonensis adult worms.

Angiostrongylus cantonensis is the main aetiological agent of eosinophilic meningoencephalitis in humans. Several outbreaks have been documented around the world, cementing its status as an emerging global public health concern. As a result, new strategies for the diagnosis, prophylaxis and treatment of cerebral angiostrongyliasis are urgently needed. In this study, we report on the de novo assembly of the A. cantonensis transcriptome, its full functional annotation and a reconstruction of complete metabolic pathways. All results are available at AngiostrongylusDB (http://angiostrongylus.lad.pucrs.br/admin/welcome). The aim of this study was to identify the active genes and metabolic pathways involved in the mechanisms of infection and survival inside Rattus norvegicus. Among 389 metabolic mapped pathways, the blood coagulation/antithrombin pathways of heparan sulphate/heparin are highlighted. Moreover, we identified genes codified to GP63 (leishmanolysin), CALR (calreticulin), ACE (peptidyl-dipeptidase A), myoglobin and vWD (von Willebrand factor type D domain protein) involved in the infection invasion and survival of the parasite. The large dataset of functional annotations provided and the full-length transcripts identified in this research may facilitate future functional genomics studies and provides a basis for the development of new techniques for the diagnosis, prevention and treatment of cerebral angiostrongyliasis.

3-Hydroxybenzaldehyde and 4-Hydroxybenzaldehyde enhance survival of mouse astrocytes treated with Angiostrongylus cantonensis young adults excretory/secretory products

BackgroundHuman cerebral angiostrongyliasis, induced by Angiostrongylus cantonensis, is an emerging disease in many parts of the world. A. cantonensis is also an important causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. 3-Hydroxybenzaldehyde (3-HBA) and 4-Hydroxybenzaldehyde (4-HBA) have been shown to increase intracellular antioxidant activity, vasculoprotective potency, wound healing, and cell migration. However, the function of 3-HBA and 4-HBA in mouse astrocytes in response to A. cantonensis young adults excretory-secretory products (ESPs) treatment remains unclear. MethodsHere, we examined the effect of 3-HBA and 4-HBA by real-time qPCR, western blotting, and cell viability assay in astrocytes after A. cantonensis young adults ESPs treatment. The real-time qPCR, western blotting were employed to detect the expression of apoptosis- and Shh pathway-related molecule. The percentage of cell viability was monitored by CCK-8 assay. ResultsWe demonstrated that expression of apoptosis-related molecules was increased in response to A. cantonensis young adults ESPs treatment. However, the cell viability of astrocytes was elevated by treatment with 3-HBA and 4-HBA. Further investigation found that 3-HBA and 4-HBA activate the Shh signaling pathway and inhibit apoptosis-related molecule expression. ConclusionsThese findings were confirmed using A. cantonensis young adults ESPs to activate apoptosis-related pathways in astrocytes. Moreover, 3-HBA and 4-HBA induced a protective phenotype through regulation of apoptosis in response to A. cantonensis young adults ESPs treatment. Hence, 3-HBA and 4-HBA represent potential therapeutic drugs for the treatment of human angiostrongyliasis.

Infection by Angiostrongylus cantonensis in both humans and the snail Achatina (Lissachatina) fulica in the city of Macapá, in the Amazon Region of Brazil.

In January and February 2019, a malacological survey was conducted in the area surrounding the residence of a 12-year-old child that had contracted cerebral angiostrongyliasis in the municipality of Macapá, capital of the Amapá State, northern Brazil. The serological examination was positive for Angiostrongylus cantonensis infection, the principal etiological agent of this parasitosis. A sample of 54 molluscs was artificially and individually digested for parasitological analysis, containing 38 specimens of Achatina fulica, nine specimens of Bulimulus tenuissimus and seven specimens of Sarasinula linguaeformis. A. fulica was the most abundant mollusc, and the only species infected with A. cantonensis, as well as presenting co-infections with other nematodes. This is the first report of cerebral angiostrongyliasis in the Amazon Region, and the first record of A. fulica infected with A. cantonensis in Amapá. These findings highlight the potential risks of human angiostrongyliasis, and the need to implement public health measures to control the spread of the disease.

Development of an immunochromatographic device to detect antibodies for rapid diagnosis of human angiostrongyliasis.

Cerebral angiostrongyliasis is a central nervous system disease caused by Angiostrongylus cantonensis and can produce eosinophilic meningitis or meningoencephalitis in humans. Sero-immunological techniques, such as the enzyme-linked immunosorbent assay (ELISA) and immunoblotting, are most commonly used for the diagnosis of human angiostrongyliasis. However, diagnosis in remote areas remains problematic because sophisticated equipment and specialized skills are required. To overcome, we have developed the immunochromatographic test (ICT) kit for rapid serological diagnosis of angiostrongyliasis through the detection of anti-A. cantonensis-specific antibodies in human serum. A recombinant A. cantonensis galectin-2 (rAcGal2) from young adult female worms was used as an antigen for the ICT kit development. Diagnostic values were evaluated and compared using the ELISA. The sensitivity, specificity and positive and negative predictive values of the ICT kit were 87.0, 96.5, 94.6 and 91.4%, respectively, and those of the ELISA were 91.0, 97.2, 95.8 and 94.0%, respectively. The concordance of the ICT kit was 93.9%. We, thus, determined that the ICT kit is sensitive and specific and provides reliable diagnostic results. It is rapid and simple to perform and can be utilized for both point-of-care diagnosis in the bedside laboratory and epidemiological surveys in endemic regions where access to diagnostic equipment is limited.

Magnetic resonance imaging findings and clinical manifestations in cerebral angiostrongyliasis from Dali, China.

PurposeTo analyze magnetic resonance imaging (MRI) findings and clinical diagnosis and treatment data relating to Angiostrongylus cantonensis infection to gain insight into the disease.Materials and MethodsWe retrospectively analyzed the epidemiology, clinical manifestations, diagnosis and treatment data, imaging manifestations, and outcomes of 27 patients who were clinically diagnosed with angiostrongyliasis and who underwent contrast‐enhanced brain MRI.ResultsPatients with A. cantonensis infection had a history of eating raw mollusks in the endemic area, and they mainly presented with dizziness and headache of varying degrees and vomiting (n = 7). Laboratory examinations revealed increased peripheral blood and cerebrospinal fluid (CSF) eosinophils, as well as increased CSF protein levels. Brain MRI findings mainly included eosinophilic meningitis, whereas linear or nodular enhancement of the pia mater was observed in enhanced T1‐weighted and fluid‐attenuated inversion recovery images, accompanied by encephalitis or vasculitis. Meningitis manifested as multiple, thickened flow voids around the meninges, and contrast‐enhanced scans showed substantial enhancement in intracranial dilated and hyperplastic blood vessels.ConclusionThe possibility of A. cantonensis infection should be considered in the effective use of albendazole or mebendazole as a treatment. Combining clinical history with laboratory examination is helpful in diagnosing A. cantonensis infection. A final definite diagnosis can be confirmed by detecting larvae in the CSF. The administration of corticosteroids during pathogen therapy can substantially reduce the therapeutic response.

Temporal-spatial pathological changes in the brains of permissive and non-permissive hosts experimentally infected with Angiostrongylus cantonensis

Human cerebral angiostrongyliasis becomes an emerging disease in many parts of the world. By postmortem examination, Angiostrongylus cantonensis have been reported to cause severe pathological changes in the central nervous system. The present study was designed to determine the temporal-spatial pathological changes through experimental infections and histopathological examination of permissive (SD rats) and non-permissive (ICR mice) hosts. After infecting SD rats with 25, 50, or 100 third-stage larvae (L3) and ICR mice with 25 L3, one animal from each group was sacrificed daily from day 1 to day 30 post-infection. Each rat brain was cut into six sections and mouse brain into five sections. These sections were stained with haematoxylin and eosin and examined microscopically. Eosinophilic meningitis was found to be the most commonly pathological change and occurred on day 17 post-infection in rats with 25 L3, day 9 in the 50- or 100-L3 groups, and day 12 in infected mice. Thickness of the meninges increased 9–24 folds in infected rats and 89 folds in an infected mouse on day 28. Encephalitis, congestion, perivascular cuffing, and haemorrhage were revealed in infected mice and rats with 100 L3. Fifth-stage larvae were frequently observed in the meninges but occasionally in the parenchyma. Significant correlations between meningitis and presence of larvae in the meninges were found in the three infected rat groups but not in the infected mice. The results indicate that the clinical course of A. cantonensis infection is not self-limited but becomes more severe with the intensity of infection.

Dot immunogold filtration assay (DIGFA) for the rapid detection of specific antibodies against the rat lungwormAngiostrongylus cantonensis(Nematoda: Metastrongyloidea) using purified 31-kDa antigen

A rapid dot immunogold filtration assay (DIGFA) was adopted for specific immunodiagnosis of human cerebral angiostrongyliasis, using purified 31-kDa glycoprotein specific to Angiostrongylus cantonensis as diagnostic antigen and protein A colloidal gold conjugate as antigen-antibody detector. A total of 59 serum samples were assayed - 11 samples from clinically diagnosed patients with detectable A. cantonensis-specific antibody in immunoblotting; 23 samples from patients with other related parasitic diseases, i.e. gnathostomiasis (n=8), cysticercosis (n=5), toxocariasis (n=2), filariasis (n=4), paragonimiasis (n=2) and malaria (n=2); and 25 samples from normal healthy subjects. The sensitivity and specificity of DIGFA to detect anti-A. cantonensis specific antibodies in serologically confirmed angiostrongyliasis cases, were both 100%. No positive DIGFA was observed in cases with other parasitic diseases, and the healthy control subjects. The 3-min DIGFA is as sensitive and specific as the 3-h immunoblot test in angiostrongyliasis confirmed cases that revealed a 31-kDa reactive band. The gold-based DIGFA is more rapid and easier to perform than the traditional enzyme-linked immunosorbent assay (ELISA). The test utilizing purified A. cantonensis antigen is reliable and reproducible for specific immunodiagnosis of human infection with A. cantonensis - thus can be applied as an additional routine test for clinical diagnostic support. Large-scale sero-epidemiological studies in endemic communities in north-east Thailand are under way to evaluate its usefulness under field conditions.

The 31-kDa Antigen of Angiostrongylus cantonensis Comprises Distinct Antigenic Glycoproteins

Human angiostrongyliasis results from accidental infection with Angiostrongylus, an intra-arterial nematode. Angiostrongylus cantonensis infections result in eosinophilic meningitis, and A. costaricensis infections cause eosinophilic enteritis. Immunological methodologies are critical to the diagnosis of both infections, since these parasites cannot be isolated from fecal matter and are rarely found in cerebrospinal fluid samples. A. costaricensis and A. cantonensis share common antigenic epitopes which elicit antibodies that recognize proteins present in either species. Detection of antibodies to a 31-kDa A. cantonensis protein present in crude adult worm extracts is a sensitive and specific method for immunodiagnosis of cerebral angiostrongyliasis. The objective of the present work was to isolate and characterize the 31-kDa proteins using soluble protein extracts derived from adult female worms using both one- (1DE) and two-dimensional (2DE) gel electrophoresis. Separated proteins were blotted onto nitrocellulose and probed using sera from infected and non-infected controls. The 31-kDa band present in 1DE gels and the 4 spots identified in 2DE gels were excised and analyzed by electrospray ionization mass spectrometry. Using the highest scores obtained following Mascot analysis, amino acid sequences were obtained that matched four unique proteins: tropomyosin, the 14-3-3 phosphoserine-binding protein, a protein containing a nascent polypeptide-associated complex domain, and the putative epsilon subunit of coatomer protein complex isoform 2. Oxidative cleavage of diols using sodium m-periodate demonstrated that carbohydrate moieties are essential for the antigenicity of all four spots of the 31-kDa antigen. In this article we describe the identification of the 31-kDa antigen, and provide DNA sequencing of the targets. In conclusion, these data suggest that reactivity to the 31-kDa proteins may represent antibody recognition of more than one protein, and recombinant protein-based assays for cerebral angiostrongyliasis diagnosis may require eukaryotic expression systems to maintain antigenicity.

Seroprevalence of Angiostrongylus cantonensis in Wild Rodents from the Canary Islands

Background Angiostrongylus cantonensis is a lungworm of rats (Muridae) that is the causative agent of human cerebral angiostrongyliasis. The life cycle of A. cantonensis involves rats and mollusks as the definitive and intermediate hosts, respectively. This study was designed to increase the knowledge about the occurrence and distribution of A. cantonensis in its definitive host in the Canary Islands, using parasitological and serological analysis in different areas and age groups.Methodology/Principal FindingsBetween 2009 and 2010, 54 black rats (Rattus rattus) from Tenerife were captured from six human-inhabited areas and sera samples were obtained. The lung nematodes were identified by morphological and molecular tools as A. cantonensis. The 31-kDa glycoprotein antigen was purified from A. cantonensis adult worms by electrophoresis and electroelution. Of the 54 tested rodents, 30 showed IgG antibodies against A. cantonensis 31-kDa antigen by ELISA. Therefore, the overall seroprevalence was 55.6% (95% CI: 42.4–68). Seroprevalent rodents were found in all the 6 areas. This 31-kDa antigen was not recognized by some sera of rats infected by other helminth species (but not A. cantonensis). Seroprevalence of IgG antibodies against A. cantonensis and prevalence based on the presence of adult worms showed significant correlation (R2 = 0.954, p<0.05).Conclusions/SignificanceThe present results could indicate a high prevalence of A. cantonensis in Tenerife and suggest the inclusion of two new zones in the distribution area of the parasite. The commonness and wide distribution of A. cantonensis in rats implies the presence of intermediate hosts, indicating that humans may be at risk of getting infected.

Enzootic Angiostrongyliasis, Guangdong, China, 2008-2009

To the Editor: The nematode Angiostrongylus cantonensis was discovered in pulmonary arteries and hearts of domestic rats in Guangzhou (Canton), China, by Chen in 1935 (1). This parasite has a complex life cycle (2) and causes cerebral angiostrongyliasis after ingestion of infective larvae found in freshwater and terrestrial snails and slugs, paratenic hosts (such as freshwater fish, shrimp, frogs, and crabs), and contaminated vegetables (3). During 2000–2006, a total of 7 outbreaks of angiostrongyliasis were reported in the People’s Republic of China, including an outbreak in Zhaoqing, Guangdong Province (4–6). We conducted a survey of A. cantonensis nematodes in mollusks and rodents in Qingyuan, Guangong Province, during August 2008–October 2009. Qingyuan is located in northern Guangdong Province (23°31′–25°12′N, 111°55′–113°55′E). It is the largest city in the province. Qingyuan borders Zhaoqing on the west and Guangzhou on the south. Its climate is subtropical monsoon, and it has an average annual temperature of 20.7°C. The city has an area of 19,152.89 km2 and a population of 3.87 million. Nematode hosts were obtained in 3 counties in Qingyuan: Qingxin, Fogang, and Lianzhou. During August 2008–October 2009, we captured 288 rats of 7 species (257 Rattus norvegicus, 13 R. flavipectus, 7 R. losea; 6 R. rattus, 3 Bandicota indica, 1 R. rattus alexandrinus, and 1 Mus musculus). Rats were examined for adult A. cantonensis nematodes in pulmonary arteries and right heart cavities. Among the 288 rats examined, 27 (9.4%) from 3 species were infected with A. cantonensis adults in their cardiopulmonary systems (Table). Infected rodents were found in all 3 counties. The 27 infected rats were 25 R. norvegicus, 1 R. losea, and 1 M. musculus. R. norvegicus rats were most frequently captured in the 3 counties, and this rodent had the highest prevalence of infection. Infected B. indica rats in Lianzhou and M. musculus rats in Qingxin were also found, but the total numbers of infected animals and the prevalences are lower than that for R. norvegicus rats. On the basis of these findings, we conclude that R. norvegicus rats are the major definitive host for A. cantonensis nematodes in Qingyuan. Table Prevalence of infection with Angiostrongylus cantonensis in 3 snail species and rodents in 3 counties in Qingyuan, Guangdong Province, China, 2008–2009 Specimens from 510 snails (144 Pomacea canaliculata, 306 Achatina fulica, and 60 Bradybaena despecta) were digested with pepsin for isolation of A. cantonensis larvae (7). Metastrongylid larvae were found in 21 (4.1%) of 510 examined snails. Prevalence rates of A. cantonensis in P. canaliculata, A. fulica, and B. despecta were 8.3%, 2.0% and 5.0%, respectively. Differences between the 3 prevalence rates were significant (χ2 9.604, p<0.05). Prevalence rates in the 3 counties are shown in the Table. All 3 species of infected snails were found in Qingxin and Fogan Counties. P. canaliculata and B. despecta snails were found infected in Qingxin County. However, only A. fulica snails were found infected in Fogang. These findings are similar to those of studies conducted in Guangdong Province (8–10). Distributions of snail species among the 3 sites differed. Although all 3 species were found in Qingxin and Fogang Counties, only A. fulica snails were found in Lianzhou County. Lower temperatures in this county may contribute to this uneven distribution. Our failure to detect infected snail hosts in Lianzhou County was unexpected, and further surveys are needed to identify parasite hosts in this area. Our findings suggest that the 3 species may play a major role as intermediate hosts for A. cantonensis nematodes in human infections. Qingyuan is a natural focus for A. cantonensis nematodes. Residents in the study area frequently eat raw or undercooked snails and slugs, unaware that these animals may contain infective larvae of A. cantonensis that can cause eosinophilic meningitis. Therefore, to protect local residents from parasite infections, inhabitants of this region must be given relevant information about A. cantonensis nematodes. Control measures to control spread of this parasite must also be implemented.

Pathological changes in the brains of rabbits experimentally infected with Angiostrongylus cantonensis after albendazole treatment: histopathological and magnetic resonance imaging studies

To determine the effects of albendazole on rabbits infected with larvae of Angiostrongylus cantonensis by histopathological and magnetic resonance imaging (MRI) techniques. Male rabbits were infected with 400 A. cantonensis larvae and treated with albendazole (5 mg/kg/day) for 2-14 days on day 5, 10, 15 or 20 post-infection. Although there were pathological changes in the brains, MRI revealed unremarkable findings in the untreated group. However, the treated rabbits exhibited eosinophilic meningitis, choroid plexus inflammation, meningeal congestion, encephalitis, perivascular cuffing and meningitis, and were also found to have abnormal signal intensities on brain MR images in the 20 day post-infection treated group. Pathological changes in the brains of the treated rabbits are more severe than those without albendazole treatment, suggesting that the drug may not be very suitable for the treatment of cerebral angiostrongyliasis.

Magnetic Resonance Imaging Findings in the Brains of Rabbits Infected with Angiostrongylus cantonensis: A Long-Term Investigation

Because magnetic resonance (MRI) imaging is a superior technique in delineating pathological changes in cerebral angiostrongyliasis, it should also be an optimal imaging modality in monitoring long-term changes in the brains of animals infected with Angiostrongylus cantonensis. In this study, MRI and histological techniques were used to observe the changes in the brains of 7 rabbits infected with the third-stage larvae of A. canronensis. Changes were monitored by MRI from day 0 to day 207 postinfection (PI). Hyperintense lesions on T2-weighted MR brain images were first observed on day 22 PI and hallmarks of abnormalities were noted on day 35 PI. Hyperintensities on brain MR images remained up to day 207 PI. Histological examination from days 108 to 207 PI revealed meningeal congestion, choroid plexus inflammation, infarction, granuloma with embedded larva, gliosis, and hemorrhage in the brain tissues. These findings suggest that hosts infected with A. cantonensis may undergo pathological changes in the brain tissues for more than 200 days PI. Moreover, severe abnormalities may occur as early as the fifth week PI.

Drug trials for treatment of human angiostrongyliasis.

Abdominal and cerebral angiostrongyliasis are two important infections produced by metastrongylid worms, the former occurring in Central and South America and the later in Asia and Pacific Islands. Drug treatment is a challenge since the worms and its evolving larvae live or migrate inside vessels and efficient killing of the parasites may produce more severe lesions. Larvicidal effect of certain drugs appears to be more easily accomplished but this outcome is not useful in abdominal angiostrongyliasis since clinical manifestations appear to result from sexual maturation of the worms. We review the drug trials in murine experimental models and conclude that most of them could not be considered good candidates for treatment of human infection, except for PF1022A, pyrantel and flubendazole.

Eosinophil activation, apoptosis and pathogeny in angiostrongylus cantonensis infection in the mouse

Human cerebral angiostrongyliasis becomes an emerging disease in many parts of the world. By postmortem examination, Angiostrongylus cantonensis have been reported to cause severe pathological changes in the central nervous system. The present study was designed to determine the temporal-spatial pathological changes through experimental infections and histopathological examination of permissive (SD rats) and non-permissive (ICR mice) hosts. After infecting SD rats with 25, 50, or 100 third-stage larvae (L3) and ICR mice with 25 L3, one animal from each group was sacrificed daily from day 1 to day 30 post-infection. Each rat brain was cut into six sections and mouse brain into five sections. These sections were stained with haematoxylin and eosin and examined microscopically. Eosinophilic meningitis was found to be the most commonly pathological change and occurred on day 17 post-infection in rats with 25 L3, day 9 in the 50- or 100-L3 groups, and day 12 in infected mice. Thickness of the meninges increased 9–24 folds in infected rats and 89 folds in an infected mouse on day 28. Encephalitis, congestion, perivascular cuffing, and haemorrhage were revealed in infected mice and rats with 100 L3. Fifth-stage larvae were frequently observed in the meninges but occasionally in the parenchyma. Significant correlations between meningitis and presence of larvae in the meninges were found in the three infected rat groups but not in the infected mice. The results indicate that the clinical course of A. cantonensis infection is not self-limited but becomes more severe with the intensity of infection.