Eosinophilic meningitis caused by Angiostrongylus cantonensis associated with eating raw snails: correlation of brain magnetic resonance imaging scans with clinical findings

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Human infection occurs after ingestion of the worms in raw snails or fish that serve as intermediate hosts. Two outbreaks of central nervous system infection with A. cantonensis occurred in Kaoshiung, Taiwan, during 1998 and 1999 among Thai laborers who ate raw snails. A detailed clinical studies of 17 of these patients was conducted, including study of 13 patients who underwent magnetic resonance imaging (MRI) scans of the brain. The MRI scans revealed high signal intensities over the globus pallidus and cerebral peduncle on T1-weighted imaging, leptomeningeal enhancement, ventriculomegaly, and punctate areas of abnormal enhancement within the cerebral and cerebellar hemisphere on gadolinium-enhancing T1 imaging, and a hyperintense signal on T2-weighted images. There was a significant correlation between severity of headache, cerebrospinal fluid (CSF) pleocytosis, and CSF and blood eosinophilia with MRI signal intensity in T1-weighted imaging (P < 0.05). Eosinophilic meningitis produced by A. cantonensis needs to added to the list of causes of hyperintense basal ganglia lesions found on T1-weighted MRI scans in tropical countries.     

Encephalitis caused by Angiostrongylus cantonensis after eating raw frogs mixed with wine as a health supplement

Angiostrongylus cantonensis also known as the rat lungworm, is prevalent in the Pacific Islands and southeast Asia and is the most common cause of eosinophilic meningitis in humans. Although frogs and toads are known as paratenic hosts of A. cantonensis, they are rarely reported as the infectious source of human angiostrongyliasis. We report a case of encephalitis caused by Angiostrongylus cantonensis after eating raw frogs mixed with wine as a health supplement. Prednisolone at a dose of 1 mg/kg/day was prescribed for 14 days successfully. We advise that travelers and residents of endemic areas should avoid eating raw frogs and a public caution on the danger of eating raw wild animal products or the whole animal is recommended to alleviate such accidental infection.     

Eosinophilic meningitis: a suspected case of angiostrongylosis found in Shizuoka Prefecture, Honshu, Japan.

A patient with eosinophilic meningitis in Shizuoka Prefecture, Honshu, Japan had nausea, vomiting and headache on admission; laboratory examinations revealed leukocytosis with eosinophilia. Eight days later neck stiffness appeared. Lumbar puncture showed an increase of the initial pressure in association with eosinophilic pleocytosis in the spinal fluid. The possibility of angiostrongylosis was considered because the patient had eaten raw slugs for 4 years as a remedy for lumbago. Although the serum contained cross-reactive antibodies against Toxocara canis, positive reactions to Angiostrongylus cantonensis antigens were observed in all of the immunological tests made. These observations, together with results of epidemiological studies in Honshu carried out by other investigators, suggest that the present case of eosinophilic meningitis may have been caused by A. cantonensis. One previous case has been reported from Honshu Island, Japan.     

Cluster of eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in French policemen troop returning from the Pacific Islands

BACKGROUND: Outbreaks of eosinophilic meningitis are reported rarely, even in regions of endemic infestation with the roundworm Angiostrongylus cantonensis, such as the Pacific Basin. We report a cluster of eosinophilic meningitis presumably attributable to A. cantonensis among French policemen returning from French Polynesia. METHODS: A retrospective cohort study among French policemen who had stayed in Tahiti was conducted using a clinical definition of eosinophilic meningitis that included severe headache within 30 days after return and eosinophilia, and who consumed locally exotic ethnic dishes with uncooked freshwater prawns. RESULTS: Five persons met the case definition for eosinophilic meningitis. Corticosteroid therapy associated with antihelminthic regimen led to improvement of symptoms in one patient. Other patients were treated with albendazole alone. All patients recovered. CONCLUSION: Among travellers at risk, the presence of severe headache and eosinophilia combined with a consistent exposure history to exotic food should alert to the possibility of A. cantonensis infestation. Travellers should be aware of the risk of infection associated with eating exotic ethnic dishes.     

Outbreak of eosinophilic meningitis associated with drinking raw vegetable juice in southern Taiwan

The most common cause of eosinophilic meningitis is the rat lungworm Angiostrongylus cantonensis a parasite that is endemic in the southeast Asian and Pacific regions. Outbreaks of eosinophilic meningitis associated with drinking raw vegetable juice are rarely reported, even in regions of endemic infection. We performed a cohort study among Taiwanese with eosinophilic meningitis who drank raw vegetable juice within three months of the onset of the outbreak. Clinical manifestations, laboratory examinations, and outcomes were prospectively followed. Five native Taiwanese met the case definition of eosinophilic meningitis. Specific antibodies to A. cantonensis were detected in the serum of five of the patients and in the cerebrospinal fluid (CSF) of four of the patients. Central nervous system manifestations included headache (n = 5 [100%]), Brudzinski's sign/stiff neck (n = 5 [100%]), hyperesthesia/paresthesias (n = 5 [100%]), and cranial nerve palsy (n = 1 [20%]). Laboratory findings included peripheral (n = 5 [100%]) and CSF eosinophilia (n = 4 [80%]), transient increases in the white blood cell count (n = 1 [20%]), and in serum levels of creatine kinase (n = 1 [20%]). Meningeal enhancement, as well as high signal intensity, at the subcortical white matter on T2 weighted and fluid attenuated inversion recovery images were observed on magnetic resonance imaging in four patients. There were three episodes of relapse during treatment and all resolved with after a lumbar puncture and/or administration of steroids. At the 12-month follow up, all five patients had recovered without neurologic sequelae. Risk factors identification showed that consumption of raw vegetable juice was associated with illness (Pearson correlation test r = 0.867, P = 0.01). There was association between the presence of raw vegetable juice and CSF eosinophilia (Spearman's correlation test r = 0.816, P = 0.004).     

Eosinophilic meningitis due to Angiostrongylus cantonensis in a returned traveler: case report and review of the literature.

Angiostrongylus cantonensis, the rat lungworm, is the principal cause of eosinophilic meningitis worldwide, and the increase in world travel and shipborne dispersal of infected rat vectors has extended this parasite to regions outside of its traditional geographic boundaries. We report a case of eosinophilic meningitis due to A. cantonensis in a patient who recently returned from a trip in the Pacific.     

广州管圆线虫病的诊断和药物治疗研究现状

广州管圆线虫病是由广州管圆线虫引起的一种人兽共患病。人是广州管圆线虫的非正常宿主，其幼虫侵入人体后，进入中枢神经系统，可引起嗜酸性粒细胞增多性脑膜炎或脑炎，对人体危害很大。该病主要流行于热带和亚热带地区，东南亚和太平洋诸岛多见。该文总结了广州管圆线虫病的诊断和治疗的研究现状。     

广州管圆线虫感染致病机制的研究进展

广州管圆线虫病是因感染了广州管圆线虫后其幼虫移行至宿主中枢神经系统,从而引起以嗜酸性粒细胞增多为特征、以脑炎和脑膜脑炎为主要临床表现的一种危害严重的食源性寄生虫病,阐明其致病机制对于广州管圆线虫病防治具有重要意义。本文主要就广州管圆线虫感染引起嗜酸性粒细胞增多性脑炎和脑膜脑炎机制研究进展作一综述。     

广州管圆线虫病的免疫学诊断研究进展

广州管圆线虫病主要在东南亚及太平洋诸岛流行。广州管圆线虫为引起嗜酸性粒细胞性脑脊膜炎或脑膜脑炎的主要病原体。近年来随着人们饮食习惯的改变,该病的流行呈上升趋势。广州管圆线虫病主要依靠从病人脑脊液中找到虫体确诊,但虫体检出率很低,免疫诊断抗原的提纯以及免疫诊断方法的改进则提高了诊断的敏感性和特异性,为该病的诊断提供了科学的辅助手段。该文对广州管圆线虫病的免疫诊断抗原及诊断方法的研究进展作一综述。     

Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases

PURPOSE: To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. SUBJECTS AND METHODS: We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails (Ampullarium canaliculatus), as well as an environmental surveillance of larvae in snails. RESULTS: We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. CONCLUSION: Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.     

Eosinophilic meningitis in a child raising snails as pets

The rat lungworm (Angiostrongylus cantonensis) is the principal cause of eosinophilic meningitis or meningoencephalitis worldwide. It is endemic in Taiwan and the Asia Pacific area. We report the case of a 10-year-old boy who was referred to us suffering from intermittent headache, low-grade fever and blurred vision of 4-5 days' duration. He had been treated for gastroenteritis just prior to referral. The patient's history was unremarkable, except that he raised snail (Ampullarium canaliculatus) as pet at home. On physical examination, the patient's consciousness was alert and well oriented. No papilledema was found on fundal examination. The neurological examination revealed normal cranial nerve function, mild weakness of both lower limbs and normal deep tendon reflexes, but positive Babinski and Kernig signs. Laboratory findings showed peripheral eosinophilia, elevated immunoglobulin E level, cerebrospinal fluid eosinophilic pleocytosis and the presence of stage 3 A. cantonensis larvae, which confirmed the diagnosis of eosinophilic meningitis. A 2-week course of mebendazole combined the glucocorticosteroids was beneficial in relieving headache, paresthesia and the other eosinophilic meningitis symptoms in the patient.     

A case of eosinophilic meningitis due to Angiostrongylus cantonensis]

We report a case of eosinophilic meningitis caused by Angiostrongylus cantonensis. This patient, a 50-year-old male, had been eating uncooked slugs for 40 years. His chief complaints on admission were headache, fever and general fatigue. Neurological examination and CT findings were normal, but the CSF contained increased cells, most of which were eosinophilic cells. The presence of eosinophilic cells in the CSF is by itself abnormal. We therefore suspected eosinophilic meningitis and performed immunological tests. Since the gelatin particle method and immunological antigen antibody reaction were positive. We diagnosed the patient as having eosinophilic meningitis caused by Angiostrongylus cantonensis. There are only 27 reported cases of this disease in Japan, and most of them have been reported in Okinawa-Prefecture.     

Epidemiologic studies of eosinophilic meningitis in southern Taiwan.

A study of the epidemiologic characteristics of 125 cases of eosinophilic meningitis or meningoencephalitis, probably caused by Angiostrongylus cantonensis, which occurred in southern Taiwan in 1968 and 1969 revealed a close association of the disease with the rainy season. In contrast to findings in other geographic areas, most such cases in this study occurred among children. A higher attack rate was observed among aborigines than among descendants of mainland Chinese. Most patients had eaten the giant African snail, Achatina fulica, prior to their illness and this mollusc was commonly found infected with third-stage larvae of A. cantonensis. However, in almost all instances the snail was eaten after it had been thoroughly cooked and examination of cooked snail meat revealed only dead larvae. It is suspected that patients became infected by inadvertently ingesting A. cantonensis larvae liberated when the snails were prepared for consumption.     

大理市1起食用螺肉引起的广州管圆线虫病暴发调查

目的 调查2011年3月大理市1起嗜酸性细胞增多性脑膜炎暴发的原因。 方法 对集体进餐的18人进行回顾性调查, 对住院病例进行病历资料分析, 核实诊断。通过线索调查, 对未住院治疗的患者进行个案调查。同时, 检测大理市市售福寿螺是否感染广州管圆线虫幼虫。 结果 18人中16人进食福寿螺, 9人发病, 发病率为56.3%; 未食螺肉的2人均未发病。7人检测广州管圆线虫抗体, 3人阳性, 阳性率为42.9%。福寿螺的来源地为集贸市场, 而同期福寿螺监测资料显示其感染率达7.3%。 结论 根据流行病学调查、 临床表现、 实验室检查, 确定此次广州管圆线虫病暴发由食用感染广州管圆线虫的福寿螺肉所致     

Angiostrongylus cantonensis in the cerebrospinal fluid of an adult male patient with eosinophilic meningitis in Thailand.

A living, fifth-stage female Angiostrongylus cantonensis 5 mm in length was discovered in the cerebrospinal fluid of a 21-year-old Thai male with eosinophilic meningitis, the second such case to be recorded from Thailand.     

Horizontal conjugate gaze palsy in eosinophilic meningitis

Two cases of eosinophilic meningitis who presented with headache and strabismus are reported. Pertinent physical examination revealed unilateral horizontal conjugate gaze palsy with absence of doll's eye maneuver and hemiparesis. The etiologic agent of eosinophilic meningitis is presumed to be Angiostrongylus cantonensis and the infected location that produce horizontal conjugate gaze palsy was a pontine lesion.     

Comparative efficacies of albendazole and the Chinese herbal medicine long-dan-xie-gan-tan, used alone or in combination, in the treatment of experimental eosinophilic meningitis induced by Angiostrongylus cantonensis

Angiostrongylus cantonensis, the rat lungworm, is the principal cause of human eosinophilic meningitis or meningoencephalitis world-wide. In the present study, the efficacies of early-stage treatment with the Chinese herbal medicine long-dan-xie-gan-tan (LDXGT) and albendazole, used alone or in combination, were evaluated in BALB/c mice with A. cantonensis-induced dysfunction of the blood-central-nervous-system barrier and eosinophilic meningo-encephalitis. Indicators of the therapeutic effect included worm recovery, histopathological scores for the meningitis, assays of tissue-type plasminogen activator (PA), urokinase-type PA and matrix metalloproteinase-9 (MMP-9) in the brain, the ratio between albumin concentrations in the cerebrospinal fluid (CSF) and serum, and counts of eosinophils in the CSF. Combined treatment with albendazole and LDXGT gave better results than monotherapy based on either drug, apparently inhibiting eosinophilic meningitis via antagonists of the PA/MMP-9 system. LDXGT may have a therapeutic role in reducing inflammatory reaction in the subarachnoid space. Monotherapy with such an anti-inflammatory drug may relieve the symptoms of mild infection and the host's immune responses to A. cantonensis larvae. In severe infection, however, co-therapy with an anthelmintic (to kill the larvae) and an anti-inflammatory agent (to provide symptomatic relief) is probably a better approach. The therapeutic strategy should be tailored to the severity of the illness and the numbers of eosinophils in the CSF.     

Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood-brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis

To evaluate possible blood-brain barrier (BBB) dysfunction caused by matrix metalloproteinase-9 (MMP-9) and its regulation by tissue inhibitors of metalloproteinase (TIMPs) in patients with eosinophilic meningitis caused by infection with Angiostrongylus cantonensis, 40 patients and 28 controls were included in this study. Concentrations of MMP-2, MMP-9, TIMP-1, and cerebrospinal fluid (CSF):serum albumin ratios (Q(Alb) values) were significantly increased in patients compared with controls. However, concentrations of TIMP-4 were significantly lower in patients. In contrast to MMP-2, proteolytic activity of MMP-9 detected by gelatin zymography was only observed in patients with eosinophilic meningitis. We detected higher levels of antibodies specific for A. cantonensis and higher Q(Alb) values and MMP-9 concentrations in CSF of patients with eosinophilic meningitis, Furthermore, the increase in the Q(Alb) value was significantly correlated with the increase in MMP-9 in patients. In parallel with CSF MMP-9, patients also showed an increase in CSF leukocyte counts. Gradual decreases in levels of Q(Alb), MMP-9, and TIMP-1 and increases in levels of TIMP-4 were observed in six patients during recovery from eosinophilic meningitis. These results suggest that the source of MMP-9 in CSF of patients with eosinophilic meningitis was probably associated with leukocytes migrating from peripheral blood to CSF. Activity of MMP-9 in CSF of patients could not be completely inhibited because of the decrease of TIMP-4, which may cause BBB dysfunction, as shown by higher Q(Alb) values in patients.     

广州管圆线虫病误诊为结核性脑膜炎2例报告并文献复习

目的探讨广州管圆线虫病容易出现误诊的原因及诊断方法。方法对2例误诊为结核性脑膜炎患者的诊疗过程结合文献综合分析。结果2例病人均因未询问出病史、第1次化验时血嗜酸性粒细胞分类正常、脑脊液化验与结脑类似而误诊。结论仔细询问病史、认真查体,临床症状与影像学检查结合血特异性抗体检测可有效地避免误诊、误治。     

The small subunit (SSU) ribosomal (r) RNA gene as a genetic marker for identifying infective 3rd juvenile stage Angiostrongylus cantonensis

We have developed a molecular method using PCR-direct sequencing to identify the infective 3rd juvenile stage of Angiostrongylus cantonensis, a nematode parasite of rodents that can accidentally infect humans and cause eosinophilic meningitis. We demonstrate that the 5' end of the small subunit (SSU) ribosomal (r) RNA gene is a suitable marker to identify A. cantonensis and distinguish it from other closely related Angiostrongylus species. When the SSU rRNA marker was employed on nematode populations extracted from the black slug Laevicaulis altae collected in 2 test sites in the Philippines, the infective 3rd juvenile stage A. cantonensis was detected without difficulty. The phylogenetic position of other non-angiostrongylid nematodes isolated was also determined. The molecular technique developed in this study provides a rapid and accurate method for the identification of A. cantonensis when morphological identification proves difficult or inadequate.