Case Report: Protracted Eosinophilic Meningitis due to Probable Angiostrongyliasis.

Eosinophilic meningitis is classically caused by Angiostrongylus cantonensis. Treatment usually includes supportive care and corticosteroids. Anthelminthic drugs are often avoided because of the risk of an inflammatory reaction to dying larvae. The duration of symptoms in most cases is up to a few weeks. We describe a case of eosinophilic meningitis, likely due to Angiostrongylus spp. infection, with recurrent symptoms and persistent cerebrospinal fluid eosinophilia despite corticosteroid treatment, over a period of almost 5 months. This only resolved after treatment with albendazole.

The metagenomic next-generation sequencing in diagnosing central nervous system angiostrongyliasis: a case report.

BACKGROUNDS: The incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests. CASE PRESENTATION: A 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations. CONCLUSIONS: The case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

El riesgo de parasitismo por Angiostrongylus cantonensis: una problemática reemergente en Cuba / The risk of parasitism by Angiostrongylus cantonensis: a re-emerging problem in Cuba / O risco de parasitismo devido a Angiostrongylus cantonensis: um problema reemergente em Cuba

RESUMEN Introducción: El riesgo de parasitismo por Angiostrongylus cantonensis transmitido por el caracol gigante africano es una problemática reemergente en Cuba. Objetivo: Sistematizar contenidos esenciales relacionados con el caracol gigante africano y el parásito Angiostrongylus cantonensis, el riesgo de meningitis eosinofílica y su manejo. Método: En el Hospital General Docente "Dr. Agostinho Neto", entre septiembre y diciembre de 2019 se hizo una revisión narrativa sobre el tema a través de una búsqueda en bases de datos electrónicas (Biblioteca Virtual en Salud): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Resultados: La información se estructuró en caracterización del caracol gigante africano y el riesgo de infección por Angiostrongylus cantonensis en Cuba, patogénesis y epidemiologia de la angiostrongylosis, y diagnóstico y tratamiento de la meningitis eosinofílica por este nemátodo. Se identificaron controversias sobre los criterios diagnósticos, el protocolo de actuación para su prevención y rehabilitación, y la carencia de un instrumento para estratificar el riesgo de esta infección. Conclusiones: Se sistematizaron contenidos esenciales sobre el caracol gigante africano, lo que posibilita la preparación de los profesionales para incrementar la percepción del riesgo de infección por Angiostrongylus cantonensis en la población.

ABSTRACT Introduction: The risk of parasitism by Angiostrongylus cantonensis transmitted by the giant African land snail, Lissachatina fulica is a re-emerging problem in Cuba. Objective: Systematize essential contents related to the giant African land snail and the parasite Angiostrongylus cantonensis, the risk of eosinophilic meningitis and its management. Method: A narrative review was made on the subject in the Teaching General Hospital "Dr. Agostinho Neto", between September and December 2019 through a search in electronic databases (Virtual Health Library): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Results: The information was structured in the characterization of the African giant land snail and the risk of infection by Angiostrongylus cantonensis in Cuba, pathogenesis and epidemiology of angiostrongylosis, and diagnosis and treatment of eosinophilic meningitis by this nematode. Controversies were identified regarding the diagnostic criteria, the protocol of action for its prevention and rehabilitation, and the lack of an instrument to stratify the risk of this infection. Conclusions: Essential content on the giant African land snail was systematized, enabling the preparation of professionals to increase the perception of the risk of infection by Angiostrongylus cantonensis in the population.

RESUMO Introdução: O risco de parasitismo causado por Angiostrongylus cantonensis transmitido pelo caracol gigante africano é um problema reemergente em Cuba. Objetivo: Sistematizar conteúdos essenciais relacionados ao caracol gigante africano e ao parasita Angiostrongylus cantonensis, ao risco de meningite eosinofílica e seu manejo. Método: No Hospital Geral de Ensino "Dr. Agostinho Neto", entre setembro e dezembro de 2019, foi realizada uma revisão narrativa do assunto através de uma busca em bases de dados eletrônicas (Biblioteca Virtual em Saúde): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Resultados: As informações foram estruturadas na caracterização do caracol gigante africano e no risco de infecção por Angiostrongylus cantonensis em Cuba, patogênese e epidemiologia da angiostrongilose, diagnóstico e tratamento da meningite eosinofílica por esse nematóide. Foram identificadas controvérsias sobre os critérios diagnósticos, o protocolo de ação para sua prevenção e reabilitação e a falta de um instrumento para estratificar o risco dessa infecção. Conclusões: Foram sistematizados conteúdos essenciais sobre o caracol gigante africano, o que possibilita a preparação de profissionais para aumentar a percepção do risco de infecção por Angiostrongylus cantonensis na população.

Diagnosing and Understanding Angiostrongyliasis, A Zoonotic Cause of Meningitis.

Eosinophilic meningitis caused by Angiostrongylus cantonensis is spreading worldwide, and it can manifest as a severe neurological disease. Angiostrongyliasis is a food- and water-borne parasitosis that usually exhibits a seasonal and circumscribed geographical distribution. To improve control and treatment of these infections, further studies of transmission dynamics under natural conditions and the development of better diagnostic tools and treatment options are needed.

Susceptibility of Biomphalaria glabrata submitted to concomitant infection with Angiostrongylus costaricensis and Schistosoma mansoni / Suscetibilidade de Biomphalaria glabrata submetida à infecção concomitante com Angiostrongylus costaricensis e Schistosoma mansoni

Abstract The easy adaptation of Angiostrongylus costaricensis, nematode responsible for abdominal angiostrongyliasis to several species of terrestrial and freshwater molluscs and the differences observed in the interactions of trematodes with their intermediate hosts have induced us to study the concomitant infection of Biomphalaria glabrata with Schistosoma mansoni and A. costaricensis. Prior exposure of B. glabrata to A. costaricensis (with an interval of 48 hours), favored the development of S. mansoni, observing higher infection rate, increased release of cercariae and increased survival of molluscs, when compared to molluscs exposed only to S. mansoni. Prior exposure of B. glabrata to A. costaricensis and then to S. mansoni also enabled the development of A. costaricensis since in the ninth week of infection, higher amount of A. costaricensis L3 larvae was recovered (12 larvae / mollusc) while for molluscs exposed only to A. costaricensis, the number of larvae recovered was lower (8 larvae / mollusc). However, pre-exposure of B. glabrata to S. mansoni (with an interval of 24 hours), and subsequently exposure to A. costaricensis proved to be very harmful to B. glabrata, causing extensive mortality of molluscs, reduced pre-patent period to release cercariae and greater recovery of L3 A. costaricensis larvae.

Resumo A facilidade de adaptação do Angiostrongylus costaricensis, nematódeo responsável pela angiostrongiliase abdominal, a diversas espécies de moluscos terrestres e dulciaquícolas e as divergências observadas nas interações dos trematódeos com seus hospedeiros intermediários nos induziu a estudar a infecção concomitante de Biomphalaria glabrata com Schistosoma mansoni e A. costaricensis. A exposição prévia de B. glabrata ao A. costaricensis (com intervalo de 48 horas), favoreceu o desenvolvimento do S. mansoni observando-se elevação da taxa de infecção, maior liberação de cercárias e maior sobrevivência dos moluscos, quando comparado com os moluscos expostos somente ao S. mansoni. A exposição de B. glabrata previamente ao A. costaricensis e posteriormente ao S. mansoni também facilitou o desenvolvimento do A. costaricensis uma vez que na nona semana de infecção foi recuperada maior quantidade de larvas L3 de A. costaricensis, enquanto nos moluscos expostos somente ao A. costaricensis, o número de larvas recuperadas foi menor . Entretanto a pré-exposição de B. glabrata ao S. mansoni (com intervalo de 24 horas), e posteriormente a exposição ao A. costaricensis mostrou-se muito prejudicial à B. glabrata provocando grande mortalidade dos moluscos, redução do período pré-patente para liberação de cercárias e maior recuperação de larvas L3 de A. costaricensis.

Susceptibility of Biomphalaria glabrata submitted to concomitant infection with Angiostrongylus costaricensis and Schistosoma mansoni.

The easy adaptation of Angiostrongylus costaricensis, nematode responsible for abdominal angiostrongyliasis to several species of terrestrial and freshwater molluscs and the differences observed in the interactions of trematodes with their intermediate hosts have induced us to study the concomitant infection of Biomphalaria glabrata with Schistosoma mansoni and A. costaricensis. Prior exposure of B. glabrata to A. costaricensis (with an interval of 48 hours), favored the development of S. mansoni, observing higher infection rate, increased release of cercariae and increased survival of molluscs, when compared to molluscs exposed only to S. mansoni. Prior exposure of B. glabrata to A. costaricensis and then to S. mansoni also enabled the development of A. costaricensis since in the ninth week of infection, higher amount of A. costaricensis L3 larvae was recovered (12 larvae / mollusc) while for molluscs exposed only to A. costaricensis, the number of larvae recovered was lower (8 larvae / mollusc). However, pre-exposure of B. glabrata to S. mansoni (with an interval of 24 hours), and subsequently exposure to A. costaricensis proved to be very harmful to B. glabrata, causing extensive mortality of molluscs, reduced pre-patent period to release cercariae and greater recovery of L3 A. costaricensis larvae.

Canine neural angiostrongylosis: a case-control study in Sydney dogs.

OBJECTIVE: To determine the risk factors for canine neural angiostrongylosis in dogs domiciled in Sydney, Australia; geographic location, age, sex, neuter status, weight and breed were assessed. PROCEDURE: Case and matched-control dogs were selected from three veterinary clinics in Sydney. Conditional logistic regression was used to identify factors associated with disease status. A scan statistic was used to identify disease clusters. RESULTS: Age (young dogs) and neuter status (entire dogs) were independent risk factors for neural angiostrongylosis diagnosis, and diagnoses predominantly occurred during autumn, with some evidence of spatial clustering. CONCLUSIONS: Veterinarians in endemic areas should be aware of these risk factors when presented with suspect canine neural angiostrongylosis cases and also should consider advising clients of preventive treatment. Potential human health risks should be further investigated, because urban dog populations might represent a useful sentinel species for disease in humans.

The potential danger of eating wild lettuce: a brief review of human rat lungworm infection.

Angiostrongylus cantonensis, the causative agent of human rat lungworm disease, is the most common cause of eosinophilic meningitis worldwide and is endemic throughout Asia Pacific. It is acquired through the consumption of infected freshwater mollusks or contaminated produce. Human angiostrongyliasis is usually a self-limited disease presenting with headache and various neurologic sequelae varying from cranial nerve palsies to radiculitis and/or paresthesias. Fatal cases are rare, and manifest as fulminant meningomyeloencephalitis. The diagnosis is made through the use of clinical history, exam, and laboratory data including peripheral blood counts, cerebrospinal fluid (CSF) examinations, and serologic or molecular diagnostic techniques. Medical therapy is largely focused on symptomatic relief, and includes analgesics, lumbar puncture, and corticosteroids. In resource-limited settings, prevention is key, and the use of analgesics can provide symptomatic relief after infection. Efforts to increase disease awareness have been made in endemic areas, as evidenced by the recent Rat Lungworm Disease Scientific Workshop which was held in Honolulu in 2011. The proceedings of the workshop were published in a supplement to this journal (Hawaii J Med Public Health. Jun 2013;72(6):Supp 2). However, wilderness medicine and travel medicine specialists must also be aware of the disease, how it is contracted, its presentation, and treatment options should they encounter a patient who is in or has returned from an endemic area. This brief review highlights eosinophilic meningitis caused by A. cantonensis, including an example case, an overview of its clinical presentation, treatment options, and prevention.

Workshop on research priorities for management and treatment of angiostrongyliasis(1).

In a concluding session of the workshop, the participants developed a list of 115 research and outreach needs, outlining the top 5-7 needs in each of 8 areas (Table). For complete information, including presenter details and abstracts, visit the workshop website at www.hawaii.edu/cowielab/Angio%20website%20home.htm.

[A review of researches on Angiostrongylus cantonensis and angiostrongyliasis cantonensis: analysis of related literatures].

Angiostrongylus cantonensis is a lung worm of rat (definitive host). Human, an abnormal host, can acquire the infection by ingesting food containing the infective larvae of this worm (third-stage larvae). Although the larvae cannot develop into adult worm in human body, it moves to human brain and eyes, causing eosinophilic meningitis (EM), meningoencephalitis, or ocular angiostrongyliasis (OA). Here we review papers related to Angiostrongylus cantonensis and angiostrongyliasis cantonensis which were published in recent ten years, and identify the main institutes and principal investigators (PI) who are researching Angiostrongylus cantonensis. We also outline the advances in research on pathogen biology, pathogenesis, diagnostic techniques, epidemiology and prevention, as well as drug developed against Angiostrongylus cantonensis.

An outbreak of angiostrongyliasis cantonensis in Beijing.

An outbreak of 81 cases of angiostrongyliasis cantonensis (AC) occurred in Beijing, China, during June through September 2006. Epidemiological characteristics, clinical signs and symptoms, laboratory tests, imaging, and treatment data from the 81 AC patients were collected and analyzed. All cases had a history of eating raw freshwater snails, and acquired Angiostrongylus cantonensis as a result. The incubation period ranged from 1 to 36 days. The main symptoms were fever, severe headache, neck stiffness, and skin paresthesia. A significant increase in eosinophilia occurred in the peripheral blood of 62 cases and in cerebrospinal fluid of 64 cases; 36 patients presented a linearly enhanced abnormal signal of the leptomeninges site during a cranial MRI examination, indicative of meningitis; 18 cases had a significant nodule shadow and spot flaky ground-glass shadow on chest computerized tomography. All patients were relieved of their illness with a 7-day treatment of albendazole.

Advances in developing molecular-diagnostic tools for strongyloid nematodes of equids: fundamental and applied implications.

Infections of equids with parasitic nematodes of the order Strongylida (subfamilies Strongylinae and Cyathostominae) are of major veterinary importance. In last decades, the widespread use of drugs against these parasites has led to problems of resistance within the Cyathostominae, and to an increase in their prevalence and intensity of infection. Novel control strategies, based on improved knowledge of parasite biology and epidemiology, have thus become important. However, there are substantial limitations in the understanding of fundamental biological and systematic aspects of these parasites, which have been due largely to limitations in their specific identification and diagnosis using traditional, morphological approaches. Recently, there has been progress in the development of DNA-based approaches for the specific identification of strongyloids of equids for systematic studies and disease diagnosis. The present article briefly reviews information on the classification, biology, pathogenesis, epidemiology of equine strongyloids and the diagnosis of infections, highlights knowledge gaps in these areas, describes recent advances in the use of molecular techniques for the genetic characterisation, specific identification and differentiation of strongyloids of equids as a basis for fundamental investigations of the systematics, population biology and ecology.

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.

The involvement of CD80 and CD86 costimulatory molecules in the induction of eosinophilia in mice infected with Nippostrongylus brasiliensis.

The costimulatory signal provided by the interaction between CD28 and its ligands, CD80 and CD86, is critical for T cell activation. The requirement of CD80 and CD86 in T cell activation for eosinophilia and IgE production was examined in mice infected with the nematode parasite Nippostrongylus brasiliensis. Combined treatment with anti-CD80 and anti-CD86 suppressed eosinophilia in the blood and the small intestine and suppressed IgE production. However, administration of either anti-CD80 or anti-CD86 alone had little effect on eosinophilia and on the elevation of IgE levels. These results suggest that CD80 and CD86 costimulation is required and either CD80 or CD86 can provide a sufficient costimulatory signal for induction of eosinophilia in mice infected with N. brasiliensis.

Infectious complications of human T cell leukemia/lymphoma virus type I infection.

Infection with human T cell leukemia/lymphoma virus type I (HTLV-I) has been etiologically associated with two diseases: adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Increasing evidence suggests that HTLV-I infection may be associated with immunosuppression and, as a consequence, affect the risk and expression of several other infectious diseases, of which the best studied are strongyloidiasis, tuberculosis, and leprosy. In strongyloidiasis, coinfection with HTLV-I appears to result in a higher rate of chronic carriage, an increased parasite load, and a risk of more severe infection. In tuberculosis, a decrease in delayed-type hypersensitivity to Mycobacterium tuberculosis has been established, but whether this decrease is clinically significant has yet to be determined. In leprosy, an increased risk of disease is suggested, but the published studies are all too poorly controlled to draw definite conclusions.

Mediastinal lymph node cells of Angiostrongylus cantonensis-infected rats respond to antigens and release interleukin-5 in vitro.

The kinetics of eosinophil growth and/or survival stimulating factor (Eo-stimulating factor) production in Angiostrongylus cantonensis-infected rats was assessed by in vitro marrow cultures. When lymphocytes, obtained from cervical, mediastinal or mesenteric lymph nodes of infected WKAH rats, were cultured with A. cantonensis antigens, Eo-stimulating factor activity was detected in the conditioned media obtained only from mediastinal lymph node cells at and after 35 days p.i. Eo-stimulating factor activity in the conditioned media was not detected before or at 20 days p.i. The kinetics of the factor was, therefore, almost identical to those of eosinophilia in bone marrow and peripheral blood. This Eo-stimulating factor activity was inhibited (maximum inhibition = 73%) by anti-mouse IL-5 monoclonal antibody in a dose-dependent fashion, indicating that the factor would be, at least in part, identical to IL-5. Similar Eo-stimulating factors were also detected in the conditioned media which were obtained by stimulating spleen cells from Wistar rats at 35-45 days p.i. with Con A. These data suggest that lymphocytes in the mediastinal lymph nodes, local lymph nodes near the adult worm habitat, could play an essential role in induction of eosinophilia in A. cantonensis-infected rats.