{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:11:00Z","timestamp":1789542660286,"version":"build-2803163510"},"reference-count":20,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"The Norwegian Research Council","doi-asserted-by":"publisher","award":["248143"],"award-info":[{"award-number":["248143"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. In many low-income countries it causes large outbreaks and disproportionally affects pregnant women and their offspring. Surveillance studies to find effective preventive interventions are needed but are hampered by the lack of funding and infrastructure. Dried blood spots (DBS) offer an easier and more robust way to collect, transport, and store blood samples compared to plasma\/serum samples, and could ease some of the barriers for such studies. In this study we optimize an HEV IgG ELISA for DBS samples and validate it on 300 paired DBS and plasma samples collected in rural areas of Bangladesh from participants in a HEV vaccine study. We demonstrate that HEV IgG in blood stored as DBS is stable for two months at up to 40 \u00b0C, and for five freeze-thaw cycles. The specificity was 97% and the overall sensitivity of the DBS assay was 81%. The sensitivity was higher in samples from vaccinated participants (100%) compared to previously infected participants (59%), reflecting a positive correlation between IgG titer and sensitivity. We found a strong correlation between DBS and plasma samples with an r2 of 0.90, but with a higher degree of difference between individual paired samples. Our study shows that DBS offers a stable alternative to plasma\/serum for HEV IgG measurements and can facilitate serological studies, particularly in resource limited areas.<\/jats:p>","DOI":"10.3390\/v14112525","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T02:31:15Z","timestamp":1668479475000},"page":"2525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Stability and Feasibility of Dried Blood Spots for Hepatitis E Virus Serology in a Rural Setting"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-1622","authenticated-orcid":false,"given":"Joakim","family":"\u00d8verb\u00f8","sequence":"first","affiliation":[{"name":"Norwegian Institute of Public Health, NO-0213 Oslo, Norway"},{"name":"Department of Microbiology, Institute of Clinical Medicine, University of Oslo, NO-0424 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-5744","authenticated-orcid":false,"given":"Asma","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Clinical Medicine, University of Oslo, NO-0424 Oslo, Norway"},{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"},{"name":"International Vaccine Institute, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Zaman","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3934-7410","authenticated-orcid":false,"given":"Cathinka Halle","family":"Julin","sequence":"additional","affiliation":[{"name":"Norwegian Institute of Public Health, NO-0213 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdausi","family":"Qadri","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrine","family":"Stene-Johansen","sequence":"additional","affiliation":[{"name":"Norwegian Institute of Public Health, NO-0213 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajib","family":"Biswas","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaumik","family":"Islam","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taufiqur Rahman","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warda","family":"Haque","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Diseases Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Synne","family":"Sandbu","sequence":"additional","affiliation":[{"name":"Norwegian Institute of Public Health, NO-0213 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9259-9572","authenticated-orcid":false,"given":"Jennifer L","family":"Dembinski","sequence":"additional","affiliation":[{"name":"Norwegian Institute of Public Health, NO-0213 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5047-4982","authenticated-orcid":false,"given":"Susanne","family":"Dudman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Clinical Medicine, University of Oslo, NO-0424 Oslo, Norway"},{"name":"Oslo University Hospital, NO-0424 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nrgastro.2017.150","article-title":"Hepatitis E virus: Advances and challenges","volume":"15","author":"Nimgaonkar","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hoa, T.N., Munshi, S.U., Ngoc, K.N., Ngoc, C.L., Thanh TT, T., Akther, T., Tabassum, S., Parvin, N., Baker, S., and Rahman, M. (2021). A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255054"},{"key":"ref_3","unstructured":"Group, H.E.V.W. (2014, October 01). Recommendations of HEV Working Group on the Use of Hepatitis E Vaccine. Available online: http:\/\/www.who.int\/immunization\/sage\/meetings\/2014\/october\/3_Hep_E_vacc_WG_SAGE_Recs_final_1Oct2014.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Azman, A.S., Ciglenecki, I., Wamala, J.F., Lynch, J., Aggarwal, R., Rahman, M., Wong, S., Serafini, M., Moussa, A.M., and Dalton, H.R. (2019). Hepatitis E should be considered a neglected tropical disease. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007453"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E70","DOI":"10.1503\/cmaj.110506","article-title":"The role of seroepidemiology in the comprehensive surveillance of vaccine-preventable diseases","volume":"184","author":"Wilson","year":"2012","journal-title":"Can. Med. Assoc. J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Malsagova, K., Kopylov, A., Stepanov, A., Butkova, T., Izotov, A., and Kaysheva, A. (2020). Dried Blood Spot in Laboratory: Directions and Prospects. Diagnostics, 10.","DOI":"10.3390\/diagnostics10040248"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Amini, F., Auma, E., Hsia, Y., Bilton, S., Hall, T., Ramkhelawon, L., Heath, P.T., and Le Doare, K. (2021). Reliability of dried blood spot (DBS) cards in antibody measurement: A systematic review. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248218"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Reinhardt, B., Taylor, R., Dawkins, C., Banks, T., Watson, N., Sundaram, A., Ewing, D., and Danko, J.R. (2022). The use of dried blood spot cards to assess serologic responses of individuals vaccinated against measles, hepatitis A, tetanus, influenza and varicella zoster. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265813"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104890","DOI":"10.1016\/j.micinf.2021.104890","article-title":"Developing and validating a modified enzyme linked immunosorbent assay method for detecting HEV IgG antibody from dried blood spot (DBS) samples in endemic settings","volume":"24","author":"Sultana","year":"2022","journal-title":"Microbes Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-94-024-0942-0_13","article-title":"Prophylactic Hepatitis E Vaccine","volume":"Volume 948","author":"Zhang","year":"2016","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e033702","DOI":"10.1136\/bmjopen-2019-033702","article-title":"HEV study protocol: Design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh","volume":"10","author":"Zaman","year":"2020","journal-title":"BMJ Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/ijns1020069","article-title":"Influence of Hematocrit and Total-Spot Volume on Performance Characteristics of Dried Blood Spots for Newborn Screening","volume":"1","author":"Hall","year":"2015","journal-title":"Int. J. Neonatal Screen."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/jmv.21656","article-title":"A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries","volume":"82","author":"Bendall","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ab.2005.04.035","article-title":"The five-parameter logistic: A characterization and comparison with the four-parameter logistic","volume":"343","author":"Gottschalk","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.theriogenology.2010.01.003","article-title":"Method agreement analysis: A review of correct methodology","volume":"73","author":"Watson","year":"2010","journal-title":"Theriogenology"},{"key":"ref_16","unstructured":"Nicholas Cox, N.J., and Steichen, T. (2007). CONCORD: Stata module for concordance correlation. Statistical Software Components S404501, Boston College Department of Economics."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/jmv.24741","article-title":"Variability in the performance characteristics of IgG anti-HEV assays and its impact on reliability of seroprevalence rates of hepatitis E","volume":"89","author":"Kodani","year":"2017","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.4155\/bio.13.156","article-title":"Hemato-critical issues in quantitative analysis of dried blood spots: Challenges and solutions","volume":"5","author":"Sadones","year":"2013","journal-title":"Bioanalysis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/0004563220981106","article-title":"Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens","volume":"58","author":"Moat","year":"2021","journal-title":"Ann. Clin. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1002\/jmv.24136","article-title":"Use of a commercial ELISA for the detection of measles-specific immunoglobulin G (IgG) in dried blood spots collected from children living in low-resource settings","volume":"87","author":"Colson","year":"2015","journal-title":"J. Med. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2525\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:12Z","timestamp":1760145492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,15]]},"references-count":20,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["v14112525"],"URL":"https:\/\/doi.org\/10.3390\/v14112525","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,15]]}}}