{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:46:58Z","timestamp":1790567218514,"version":"4.1.0"},"reference-count":16,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Melioidosis, an infection with the bacterium Burkholderia pseudomallei, is highly endemic in the Top End of the Northern Territory of Australia. The indirect haemagglutination assay (IHA) is the most widely used serology test globally, but it is not standardised among the limited number of laboratories that perform it. While concerns have been raised about the sensitivity of IHA early in melioidosis infections, the advantage of IHA over more recently developed ELISAs is that testing serial dilutions allows a titre to be recorded. While in Australia a titre of 1:40 or higher is considered positive, the specificity at these low positive titres remains uncertain. However, a high titre is considered to represent recent or past true infection with B. pseudomallei, rather than cross-rection with other environmental Burkholderia species. Also, the natural history of IHA titres over time, in both asymptomatic infection and melioidosis has been little studied. We have assessed the clinical status and serology time courses of all 534 patients who had an IHA titre of 1:640 or higher, over a 20-year period. Of these, 324 (60.7%) were diagnosed with culture-confirmed melioidosis, with varying time courses of diagnosis of melioidosis in relation to the high serology. Of the 210 without confirmed melioidosis, 22 (10.5%) were considered highly likely to be melioidosis despite being culture-negative, and these were all treated as melioidosis. In the remainder, titres mostly gradually decreased over time, but the majority remained seropositive. A small number who had not been treated for melioidosis continued to have high IHA titres over years and activation from latency with a new diagnosis of melioidosis was occasionally documented. This study highlights the importance of a full clinical workup in those found to have high titre melioidosis serology as well as subsequent close clinical surveillance and where resources allow, yearly IHA in those not confirmed or treated as melioidosis.<\/jats:p>","DOI":"10.3390\/pathogens14020165","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Implications of High Melioidosis Serology Indirect Haemagglutination Assay Titre: A 20-Year Retrospective Study from the Top End of the Northern Territory, Australia"],"prefix":"10.3390","volume":"14","author":[{"given":"Cassandra","family":"Ho","sequence":"first","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia"},{"name":"Northern Territory Medical Program, Flinders University, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Freeman","sequence":"additional","affiliation":[{"name":"Territory Pathology, Royal Darwin Hospital, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Woerle","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Territory Pathology, Royal Darwin Hospital, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mayo","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Baird","sequence":"additional","affiliation":[{"name":"Territory Pathology, Royal Darwin Hospital, Darwin, NT 0811, Australia"},{"name":"Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7993-820X","authenticated-orcid":false,"given":"Ella M.","family":"Meumann","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia"},{"name":"Territory Pathology, Royal Darwin Hospital, Darwin, NT 0811, Australia"},{"name":"Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-8837","authenticated-orcid":false,"given":"Bart J.","family":"Currie","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia"},{"name":"Northern Territory Medical Program, Flinders University, Darwin, NT 0811, Australia"},{"name":"Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT 0811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-023-00972-5","article-title":"Burkholderia pseudomallei and melioidosis","volume":"22","author":"Meumann","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Limmathurotsakul, D., Golding, N., Dance, D.A., Messina, J.P., Pigott, D.M., Moyes, C.L., Rolim, D.B., Bertherat, E., Day, N.P., and Peacock, S.J. (2016). Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat. Microbiol., 11.","DOI":"10.1038\/nmicrobiol.2015.8"},{"key":"ref_3","unstructured":"IHME Pathogen Core Group (2024). Global burden associated with 85 pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Infect. Dis., 24, 868\u2013895."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S1473-3099(19)30157-4","article-title":"Global burden of melioidosis in 2015: A systematic review and data synthesis","volume":"19","author":"Birnie","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1016\/S1473-3099(21)00394-7","article-title":"A call to action: Time to recognise melioidosis as a neglected tropical disease","volume":"22","author":"Savelkoel","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00006-19","DOI":"10.1128\/CMR.00006-19","article-title":"Human Melioidosis","volume":"33","author":"Gassiep","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1016\/S1473-3099(21)00022-0","article-title":"The Darwin prospective melioidosis study: A 30-year prospective, observational investigation","volume":"21","author":"Currie","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1055\/s-0034-1398389","article-title":"Melioidosis: Evolving concepts in epidemiology, pathogenesis, and treatment","volume":"36","author":"Currie","year":"2015","journal-title":"Semin. Resp. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.4269\/ajtmh.17-0998","article-title":"Antibodies in melioidosis: The role of the indirect hemagglutination assay in evaluating patients and exposed populations","volume":"99","author":"Chaichana","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1128\/CVI.00026-09","article-title":"Clinical features that affect indirect-hemagglutination-assay responses to Burkholderia pseudomallei","volume":"16","author":"Harris","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1128\/CVI.00021-13","article-title":"Surprisingly low seroprevalence of Burkholderia pseudomallei in exposed healthy adults in the Darwin region of tropical Australia where melioidosis is highly endemic","volume":"20","author":"James","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Limmathurotsakul, D., Jamsen, K., Arayawichanont, A., Simpson, J.A., White, L.J., Lee, S.J., Wuthiekanun, V., Chantratita, N., Cheng, A., and Day, N.P.J. (2010). Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012485"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4269\/ajtmh.2006.74.330","article-title":"Indirect hemagglutination assay in patients with melioidosis in Northern Australia","volume":"74","author":"Cheng","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4269\/ajtmh.24-0007","article-title":"Melioidosis and activation from latency: The \u2018time-bomb\u2019 has not occurred","volume":"111","author":"Howes","year":"2024","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.4269\/ajtmh.2006.74.1074","article-title":"Development of antibodies to Burkholderia pseudomallei during childhood in melioidosis- endemic Northeast Thailand","volume":"74","author":"Wuthiekanun","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hantrakun, V., Thaipadungpanit, J., Rongkard, P., Srilohasin, P., Amornchai, P., Langla, S., Mukaka, M., Chantratita, N., Wuthiekanun, V., and Dance, D.A.B. (2018). Presence of B. thailandensis and B. thailandensis expressing B. pseudomallei-like capsular polysaccharide in Thailand, and their associations with serological response to B. pseudomallei. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006193"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:11Z","timestamp":1760027351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,8]]},"references-count":16,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["pathogens14020165"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14020165","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,8]]}}}