Examination of Diagnostic Performance of New IgG4 Rapid Test Compared with IgG- and IgG4-ELISAs to Investigate Epidemiology of Strongyloidiasis in Northeast Thailand

Phattharaphon Wongphutorn Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand;

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Rahmah Noordin Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia;

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Nor Suhada Anuar Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia;

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Chanika Worasith Department of Adult Nursing, Faculty of Nursing, Khon Kaen University, Khon Kaen, Thailand;

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Kulthida Y. Kopolrat Faculty of Public Health, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand;

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Chutima Homwong Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand;

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Patcharaporn Tippayawat Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand;

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Anchalee Techasen Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand;

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Opal Pitaksakurat Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

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Jiraporn Sithithaworn Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand;

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Chatanun Eamudomkarn Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

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Paiboon Sithithaworn Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand;
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

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ABSTRACT.

Strongyloidiasis, caused by Strongyloides stercoralis, is a neglected tropical disease with a global distribution. The infection can be fatal in immunocompromised individuals, and accurate diagnosis leading to timely treatment can save lives. Serodiagnosis is a sensitive method for diagnosis and is recommended for screening high-risk individuals. A point-of-care rapid test will facilitate the screening activities, especially in low-resource settings. This study aims to apply a new IgG4 immunochromatographic test using S. stercoralis recombinant antigen (SsRapidĀ® cassette test) and to compare it with in-house IgG and IgG4 enzyme-linked immunosorbent assays (IgG- and IgG4-ELISAs) using native Strongyloides ratti antigen to investigate the epidemiology of strongyloidiasis in northeast Thailand. A total of 300 people participated, with 136 males and 164 females of a similar mean age. The reference tests were fecal examinations using the formalin-ethyl acetate concentration technique and an agar plate culture technique. The prevalence of S. stercoralis determined by SsRapid (81.7%) was significantly higher than that by fecal examinations (43.3%) or by antibody detection by IgG-ELISA (53.0%) or IgG4-ELISA (44.0%). The diagnostic sensitivities of SsRapid, IgG-ELISA, and IgG4-ELISA were found to be 93.9%, 77.7%, and 63.1%, respectively. The rate of positive tests by the SsRapid was significantly correlated to the levels of Strongyloides-specific IgG4 and IgG antibodies. By all diagnostic methods, male participants had a significantly higher prevalence of strongyloidiasis than females. Age was significantly associated with the concentration of specific serum IgG but not with the SsRapid grading score. In conclusion, SsRapid was shown to be a sensitive and valuable diagnostic test for the epidemiology study of strongyloidiasis.

Author Notes

Financial support: This project is funded by the National Research Council of Thailand (NRCT). P. S. is supported by the National Science, Research and Innovation Fund (NSRF), under the Basic Research Fund of Khon Kaen University through the Cholangiocarcinoma Research Institute (grant number CARI-BRF64-50). The prototype SsRapid cassette test was prepared usingthe Malaysian Ministry of Higher Education (MOHE) MyLAB grant 1/2018 (number 203.CIPPM.6730142).

Disclosure: R. Noordin and N.S. Anuar developed the SsRapid test, which has recently been licensed by Universiti Sains Malaysia (the test owner) to a diagnostic test manufacturer. The human subject protocol used in this study was approved by the Human Ethics Committee, Khon Kaen University, Thailand (reference number HE654013) according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from individual subjects from the Kamalasai district, Kalasin province, northeast Thailand. All samples were anonymized and blinded during sample analysis. The laboratory animal handling and S. ratti antigen production in Wistar rats were approved by the Institutional Animal Ethical Committee, Khon Kaen University (IACUC-KKU-99/62). The procedure strictly followed the guidelines for the Care and Use of Laboratory Animals of the National Research Council of Thailand.

Authors’ addresses: Phattharaphon Wongphutorn, Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand, E-mail: phattharaphon_w@kkumail.com. Rahmah Noordin, Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, and Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia, E-mail: rahmah8485@gmail.com. Nor Suhada Anuar, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia, E-mail: norsuhada@usm.my. Chanika Worasith, Department of Adult Nursing, Faculty of Nursing, Khon Kaen University, Khon Kaen, Thailand, E-mail: chanikawor@kku.ac.th. Kulthida Y. Kopolrat, Faculty of Public Health, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand, E-mail: kulthida.y@ku.th. Chutima Homwong, Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand, E-mail: jiffy2731@gmail.com. Patcharaporn Tippayawat, Anchalee Techasen, and Jiraporn Sithithaworn, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand, E-mails: patchatip@kku.ac.th, anchte@kku.ac.th, and jirapornsithi@gmail.com. Opal Pitaksakurat and Chatanun Eamudomkarn, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, E-mails: opalpi@kku.ac.th and chatea@kku.ac.th. Paiboon Sithithaworn, Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand, and Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, E-mail: paibsit@gmail.com.

Address correspondence to Paiboon Sithithaworn, Department of Parasitology, Faculty of Medicine, Khon Kaen University, 123 Mitraparb Road, Khon Kaen 40002, Thailand. E-mail: paibsit@gmail.com
  • 1.

    Buonfrate D et al., 2020. The global prevalence of Strongyloides stercoralis infection. Pathogens 9: 468.

  • 2.

    Krolewiecki A , Nutman TB , 2019. Strongyloidiasis: a neglected tropical disease. Infect Dis Clin North Am 33: 135–151.

  • 3.

    SchƤr F , Giardina F , Khieu V , Muth S , Vounatsou P , Marti H , Odermatt P , 2016. Occurrence of and risk factors for Strongyloides stercoralis infection in South-East Asia. Acta Trop 159: 227–238.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    SchƤr F , Trostdorf U , Giardina F , Khieu V , Muth S , Marti H , Vounatsou P , Odermatt P , 2013. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis 7: e2288.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Montes M , Sawhney C , Barros N , 2010. Strongyloides stercoralis: there but not seen. Curr Opin Infect Dis 23: 500–504.

  • 6.

    Olsen A , van Lieshout L , Marti H , Polderman T , Polman K , Steinmann P , Stothard R , Thybo S , Verweij JJ , Magnussen P , 2009. Strongyloidiasis – the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 103: 967–972.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Requena-MƩndez A , Chiodini P , Bisoffi Z , Buonfrate D , Gotuzzo E , MuƱoz J , 2013. The laboratory diagnosis and follow up of strongyloidiasis: a systematic review. PLoS Negl Trop Dis 7: e2002.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Eamudomkarn C , Ruantip S , Sithithaworn J , Techasen A , Kopoolrat KY , Worasith C , Wongphutorn P , Bethony JM , Laha TSP , 2023. Epidemiology of strongyloidiasis determined by parasite-specific IgG detections by enzyme-linked immunosorbent assay on urine samples using Strongyloides stercoralis, S. ratti and recombinant protein (NIE) as antigens in Northeast Thailand. PLoS One 18: e0284305.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Knopp S , Mgeni AF , Khamis IS , Steinmann P , Stothard JR , Rollinson D , Marti H , Utzinger J , 2008. Diagnosis of soil-transmitted helminths in the era of preventive chemotherapy: effect of multiple stool sampling and use of different diagnostic techniques. PLoS Negl Trop Dis 2: e331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Steinmann P , Zhou XN , Du ZW , Jiang JY , Wang LB , Wang XZ , Li LH , Marti HUJ , 2007. Occurrence of Strongyloides stercoralis in Yunnan Province, China, and comparison of diagnostic methods. PLoS Negl Trop Dis 1: e75.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Iamrod K et al., 2021. Development and efficacy of droplet digital PCR for detection of Strongyloides stercoralis in stool. Am J Trop Med Hyg 106: 312–319.

  • 12.

    Lodh N , Caro R , Sofer S , Scott A , Krolewiecki A , Shiff C , 2016. Diagnosis of Strongyloides stercoralis: detection of parasite-derived DNA in urine. Acta Trop 163: 9–13.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Gorgani-Firouzjaee T , Kalantari N , Javanian M , Ghaffari S , 2018. Strongyloides stercoralis: detection of parasite-derived DNA in serum samples obtained from immunosuppressed patients. Parasitol Res 117: 2927–2932.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Bisoffi Z et al., 2014. Diagnostic accuracy of five serologic tests for Strongyloides stercoralis infection. PLoS Negl Trop Dis 8: e2640.

  • 15.

    Cunha RA , de Carvalho EFG , de Sousa JEN , Costa-Cruz JM , 2017. Excretory/secretory antigens of Strongyloides venezuelensis applied to IgG detection in human strongyloidosis. Parasitol Int 66: 671–676.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Rodrigues RM , De Oliveira MC , Sopelete MC , Silva DAO , Campos DMB , Taketomi EA , Costa-Cruz JM , 2007. IgG1, IgG4, and IgE antibody responses in human strongyloidiasis by ELISA using Strongyloides ratti saline extract as heterologous antigen. Parasitol Res 101: 1209–1214.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Land KJ , Boeras DI , Chen XS , Ramsay AR , Peeling RW , 2019. REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes. Nat Microbiol 4: 46–54.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Sadaow L , Sanpool O , Rodpai R , Boonroumkaew P , Maleewong W , Intapan PM , 2020. Development of immunochromatographic device as a point-of-care tool for serodiagnosis of human strongyloidiasis cases. Eur J Clin Microbiol Infect Dis 39: 465–470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Boonroumkaew P , Sadaow L , Sanpool O , Rodpai R , Thanchomnang T , Phupiewkham W , Intapan PM , Maleewong W , 2020. Effectiveness of Strongyloides recombinant IgG immunoreactive antigen in detecting IgG and IgG4 subclass antibodies for diagnosis of human strongyloidiasis using rapid immunochromatographic tests. Diagnostics (Basel) 10: 615.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Noordin R , Anuar NS , Juri NM , Wongphutorn P , Ruantip S , Kopolrat KY , Worasith C , Sithithaworn J , Sithithaworn P , 2021. Evaluation of a rapid IgG4 lateral flow dipstick test to detect Strongyloides stercoralis infection in northeast Thailand. Am J Trop Med Hyg 105: 688–691.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Noordin R , Osman E , Anuar NS , Juri NM , Rahumatullah A , Hilmi NAA , 2021. Serum adsorption study to validate the specificity of a rapid test to detect Strongyloides stercoralis infection. Am J Trop Med Hyg 105: 1214–1217.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Yunus MH , Arifin N , Balachandra D , Anuar NS , Noordin R , 2019. Lateral flow dipstick test for serodiagnosis of strongyloidiasis. Am J Trop Med Hyg 101: 432–435.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Noordin R , Osman E , Kalantari N , Anuar NS , Gorgani-Firouzjaee T , Sithithaworn P , Juri NM , Rahumatullah A , 2022. A point-of-care cassette test for detection of Strongyloides stercoralis. Acta Trop 226: 106251.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Tamarozzi F , Longoni SS , Mazzi C , Rizzi E , Noordin R , Buonfrate D , 2022. The accuracy of a recombinant antigen immunochromatographic test for the detection of Strongyloides stercoralis infection in migrants from sub-Saharan Africa. Parasit Vectors 15: 142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Tamarozzi F et al., 2023. Accuracy, acceptability, and feasibility of diagnostic tests for the screening of Strongyloides stercoralis in the field (ESTRELLA): a cross-sectional study in Ecuador. Lancet Glob Health 11: 740–748.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Sithithaworn P , Srisawangwong T , Tesana S , Daenseekaew W , Sithithaworn J , Fujimaki YAK , 2003. Epidemiology of Strongyloides stercoralis in north-east Thailand: application of the agar plate culture technique compared with the enzyme-linked immunosorbent assay. Trans R Soc Trop Med Hyg 97: 398–402.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Elkins D , Sithithaworn P , Haswell-Elkins M , Kaewkes S , Wongratanacheewin S , Awacharagan P , 1991. Opisthorchis viverrini: relationships between egg counts, worms recovered and antibody levels within an endemic community in Northeast Thailand. Parasitology 102: 283–288.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Koga K , Kasuya S , Khamboonruang C , Sukhavat K , Ieda M , Takatsuka N , Kita K , Ohtomo H , 1991. A modified agar plate method for detection of Strongyloides stercoralis. Am J Trop Med Hyg 45: 518–521.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Eamudomkarn C , Sithithaworn P , Sithithaworn J , Kaewkes S , Sripa B , Itoh M , 2015. Comparative evaluation of Strongyloides ratti and S. stercoralis larval antigen for diagnosis of strongyloidiasis in an endemic area of opisthorchiasis. Parasitol Res 114: 2543–2551.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Eamudomkarn C et al., 2018. Diagnostic performance of urinary IgG antibody detection: a novel approach for population screening of strongyloidiasis. PLoS One 13: e0192598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Krolewiecki AJ et al., 2010. Improved diagnosis of Strongyloides stercoralis using recombinant antigen-based serologies in a community-wide study in northern Argentina. Clin Vaccine Immunol 17: 1624–1630.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    McHugh ML , 2012. Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22: 276–282.

  • 33.

    Viera AJ , Garrett JM , 2005. Understanding interobserver agreement: the kappa statistic. Fam Med 37: 360–363.

  • 34.

    Forrer A , Khieu V , Vounatsou P , Sithithaworn P , Ruantip S , Huy R , Muth S , Odermatt P , 2019. Strongyloides stercoralis: spatial distribution of a highly prevalent and ubiquitous soil-transmitted helminth in Cambodia. PLoS Negl Trop Dis 13: e0006943.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Chankongsin S , Wampfler R , Ruf MT , Odermatt P , Marti H , Nickel B , Keoluangkhot V , Neumayr A , 2020. Strongyloides stercoralis prevalence and diagnostics in Vientiane, Lao People’s Democratic Republic. Infect Dis Poverty 9: 133.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Jongsuksuntigul P , Wongsaroj T , Singthong S , Maleewong W , Intapan PM , Nilpan S , Veerakul S , 2003. Prevalence of Strongyloides stercoralis infection in Northeastern Thailand (agar plate culture detection). J Med Assoc Thai 86: 737–741.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Senephansiri P , Laummaunwai P , Laymanivong S , Boonmar T , 2017. Status and risk factors of Strongyloides stercoralis infection in rural communities of Xayaburi province, Lao PDR. Korean J Parasitol 55: 569–573.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Vonghachack Y , Sayasone S , Bouakhasith D , Taisayavong K , Akkavong K , Odermatt P , 2015. Epidemiology of Strongyloides stercoralis on Mekong islands in southern Laos. Acta Trop 141: 289–294.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Khieu V , SchƤr F , Forrer A , Hattendorf J , Marti H , Duong S , Vounatsou P , Muth S , Odermatt P , 2014. High prevalence and spatial distribution of Strongyloides stercoralis in rural Cambodia. PLoS Negl Trop Dis 8: e2854.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Tamarozzi F , Longoni SS , Mazzi C , Pettene S , Montresor A , Mahanty S , Bisoffi Z , Buonfrate D , 2021. Diagnostic accuracy of a novel enzyme-linked immunoassay for the detection of IgG and IgG4 against Strongyloides stercoralis based on the recombinant antigens NIE/SsIR. Parasit Vectors 14: 412.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Buonfrate D et al., 2019. Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. Lancet Infect Dis 19: 1181–1190.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Anuar NS , Rahumatullah A , Samsudin N , Mohamed Z , Osman E , Zakaria NZ , Ahmad H , Noordin R , 2023. Performance assessment of a lateral flow rapid test (SsRapidĀ®) compared with two commercial ELISAs in detecting Strongyloides infection. Am J Trop Med Hyg 108: 353–355.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Arifin N , Hanafiah KM , Ahmad H , Noordin R , 2019. Serodiagnosis and early detection of Strongyloides stercoralis infection. J Microbiol Immunol Infect 52: 371–378.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Munisankar S et al., 2022. Seroprevalence of Strongyloides stercoralis infection in a South Indian adult population. PLoS Negl Trop Dis 16: e0010561.

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