{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:03:32Z","timestamp":1771657412855,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hawai\u2019i State Legislature"},{"name":"Daniel K. Inouye College of Pharmacy, University of Hawai\u2019i at Hilo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Neuroangiostrongyliasis (NAS) is an emerging tropical disease in humans and some animals which is caused by infection with the parasitic nematode Angiostrongylus cantonensis. It is the leading cause of eosinophilic meningitis worldwide. Diagnoses in humans and susceptible animals are generally presumptive and easily confused with other central nervous system disorders. The 31 kDa antigen is currently the only NAS immunodiagnostic assay that has achieved 100% sensitivity. However, little is known about the humoral immune response against the 31 kDa antigen in NAS infections, which would be critical for widespread adoption of this assay. We used the Hawai\u2019i 31 kDa isolate in an indirect ELISA assay to confirm the presence of immunoglobulin IgG, IgM, IgA, and IgE isotypes in six-week post-infection plasma from lab-reared rats infected with 50 live, third-stage, A. cantonensis larvae isolated from a wild Parmarion martensi semi-slug. Our results confirmed the presence of all four isotypes against the Hawaii 31 kDa isolate, with sensitivity ranging from 22\u2013100%. The IgG isotype showed 100% sensitivity in detecting A. cantonensis infection, which validates the use of IgG indirect ELISA with 31 kDa antigen as an effective immunodiagnostic assay for rats six weeks post-infection. Given each isotype may be present at different times during NAS infections, our data provides preliminary information on the humoral immune response to A. cantonensis infection in lab-reared rats and serves as a baseline for future studies.<\/jats:p>","DOI":"10.3390\/pathogens12040625","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T02:05:31Z","timestamp":1682042731000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of Antibody Isotype Response to Angiostrongylus cantonensis in Experimentally Infected Rats (Rattus norvegicus) Using Hawai\u2019i 31 kDa Antigen in an Indirect ELISA"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1372-3286","authenticated-orcid":false,"given":"Argon","family":"Steel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai\u2019i at Hilo, 200 West Kawili St., Hilo, HI 96720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Kaluna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai\u2019i at Hilo, 200 West Kawili St., Hilo, HI 96720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-1731","authenticated-orcid":false,"given":"John","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai\u2019i at Hilo, 200 West Kawili St., Hilo, HI 96720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9824-0509","authenticated-orcid":false,"given":"Susan","family":"Jarvi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai\u2019i at Hilo, 200 West Kawili St., Hilo, HI 96720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1128\/CMR.00044-08","article-title":"Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance","volume":"22","author":"Yoshimura","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4269\/ajtmh.17-0206","article-title":"Neuroangiostrongyliasis: The \u201cSubarachnoid Phase\u201d and Its Implications for Anthelminthic Therapy","volume":"98","author":"Prociv","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0065-308X(08)60366-8","article-title":"Biology and Distribution of the Rat Lungworm, Angiostrongylus cantonensis, and Its Relationship to Eosinophilic Meningoencephalitis and Other Neurological Disorders of Man and Animals","volume":"3","author":"Alicata","year":"1965","journal-title":"Adv. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"825","DOI":"10.15585\/mmwr.mm6730a4","article-title":"Rat Lungworm Infection Associated with Central Nervous System Disease\u2014Eight U.S. States, January 2011\u2013January 2017","volume":"67","author":"Liu","year":"2018","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"608","DOI":"10.4269\/ajtmh.19-0280","article-title":"Review of Cases of Angiostrongyliasis in Hawaii, 2007\u20132017","volume":"101","author":"Johnston","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_6","first-page":"35","article-title":"Clinical Aspects of Eosinophilic Meningitis and Meningoencephalitis Caused by Angiostrongylus cantonensis, the Rat Lungworm","volume":"72","author":"Murphy","year":"2013","journal-title":"Hawaii J. Med. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1017\/S0031182016000652","article-title":"Angiostrongylus cantonensis: A Review of Its Distribution, Molecular Biology and Clinical Significance as a Human Pathogen","volume":"143","author":"Barratt","year":"2016","journal-title":"Parasitology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1751-0813.2003.tb11071.x","article-title":"Antemortem Diagnosis of Canine Neural Angiostrongylosis Using ELISA","volume":"81","author":"Lunn","year":"2003","journal-title":"Aust. Vet. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1017\/S0031182020001262","article-title":"Guidelines for the Diagnosis and Treatment of Neuroangiostrongyliasis: Updated Recommendations","volume":"148","author":"Ansdell","year":"2021","journal-title":"Parasitology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4269\/ajtmh.15-0146","article-title":"Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis","volume":"94","author":"Qvarnstrom","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1594","DOI":"10.1093\/cid\/ciaa1791","article-title":"AcanR3990 QPCR: A Novel, Highly Sensitive, Bioinformatically-Informed Assay to Detect Angiostrongylus cantonensis Infections","volume":"73","author":"Sears","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","first-page":"55","article-title":"The Current Status of Laboratory Diagnosis of Angiostrongylus cantonensis Infections in Humans Using Serologic and Molecular Methods","volume":"72","author":"Wilkins","year":"2013","journal-title":"Hawaii J. Med. Public Health"},{"key":"ref_13","first-page":"161","article-title":"Clinical Manifestations and Laboratory Diagnosis of Eosinophilic Meningitis Syndrome Associated with Angiostrongyliasis","volume":"9","author":"Cross","year":"1978","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/0035-9203(86)90324-X","article-title":"Enzyme-Linked Immunosorbent Assay (ELISA) for the Detection of Antibodies to Angiostrongylus cantonensis","volume":"80","author":"Chen","year":"1986","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_15","first-page":"55","article-title":"Isolation of Specific Antigens from Angiostrongylus cantonensis by a Combination of Preparative Isoelectric Focusing and Affinity Chromatography","volume":"3","author":"Kum","year":"1986","journal-title":"Trop. Biomed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0020-7519(91)90116-O","article-title":"Detection of Antibodies to Angiostrongylus cantonensis in Serum and Cerebrospinal Fluid of Patients with Eosinophilic Meningitis","volume":"21","author":"Yen","year":"1991","journal-title":"Int. J. Parasitol."},{"key":"ref_17","first-page":"6","article-title":"Purification of a Specific Immunodiagnostic Parastrongylus cantonensis Antigen by Electroelution from SDS-Polyacrylamide Gels","volume":"32","author":"Eamsobhana","year":"2001","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1017\/S0031182016001918","article-title":"Cross-Reactivity of the 31 KDa Antigen of Angiostrongylus cantonensis\u2014Dealing with the Immunodiagnosis of Meningoencephalitis","volume":"144","author":"Morassutti","year":"2017","journal-title":"Parasitology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF00927668","article-title":"Antibody Responses in Rats Infected with Angiostrongylus cantonensis and the Passive Transfer of Protective Immunity with Immune Serum","volume":"67","author":"Yong","year":"1982","journal-title":"Z. Parasitenkd."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0145-305X(85)90011-4","article-title":"Polyclonal B Cell Activation during the Course of Angiostrongylus cantonensis Infection","volume":"9","author":"Takai","year":"1985","journal-title":"Dev. Comp. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4269\/ajtmh.1988.39.353","article-title":"Local Antibody Production and Immune Complex Formation in Rats Experimentally Infected with Angiostrongylus cantonensis","volume":"39","author":"Kanbara","year":"1988","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_22","first-page":"62","article-title":"Time-Course Changes in Antibody Responses to Different Stages of Angiostrongylus cantonensis in Experimentally Infected Rats","volume":"35","author":"Chang","year":"1996","journal-title":"Zool. Stud."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1128\/CDLI.5.4.452-455.1998","article-title":"Intrathecal Synthesis of Immunoglobulins in Eosinophilic Meningoencephalitis Due to Angiostrongylus cantonensis","volume":"5","author":"Reiber","year":"1998","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jarvi, S.I., Cannoles, K., Eamsobhana, P., Kaluna, L.M., Shepherd, L., and Tagami, Y. (Am. J. Trop. Med. Hyg., 2023). Immunodiagnostic Detection of Angiostrongylus cantonensis Exposure on Hawaii Island Using Isogeographical 31 KDa Antigen, Am. J. Trop. Med. Hyg., in press.","DOI":"10.4269\/ajtmh.22-0643"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1017\/S0031182019000908","article-title":"Validation of a Death Assay for Angiostrongylus cantonensis Larvae (L3) Using Propidium Iodide in a Rat Model (Rattus norvegicus)","volume":"146","author":"Jarvi","year":"2019","journal-title":"Parasitology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4269\/ajtmh.18-0242","article-title":"Estimating Human Exposure to Rat Lungworm (Angiostrongylus cantonensis) on Hawaii Island: A Pilot Study","volume":"102","author":"Jarvi","year":"2020","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_27","first-page":"1","article-title":"Identification of Parastrongylus cantonensis Specific Antigens for Use in Immunodiagnosis","volume":"1","author":"Eamsobhana","year":"1997","journal-title":"Int. Med. Res. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1017\/S0031182015000554","article-title":"Comparison of Coprological, Immunological and Molecular Methods for the Detection of Dogs Infected with Angiostrongylus Vasorum before and after Anthelmintic Treatment","volume":"142","author":"Schnyder","year":"2015","journal-title":"Parasitology"},{"key":"ref_30","first-page":"1","article-title":"Rat Lungworm Disease for the Veterinary Professional","volume":"VE-2","author":"Odani","year":"2019","journal-title":"CTAHR Vet. Ext."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/4\/625\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:18Z","timestamp":1760124018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/4\/625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["pathogens12040625"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12040625","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}