{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:43:59Z","timestamp":1790635439759,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sindbis virus (SINV) is a mosquito-borne alphavirus that is widely distributed worldwide. Little is known about the febrile and neurological disease burden due to SINV in South Africa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Clinical samples of patients with acute febrile disease of unknown cause (AFDUC) were collected through the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents at three sentinel hospital surveillance sites in South Africa. In total, 639 patients were screened using a PCR-based macroarray that can simultaneously detect nucleic acids of 30 pathogens, including SINV, from January 2019 to December 2020. Serum samples were randomly selected from the arbovirus season (January\u2013June) and also screened with a commercial indirect immunofluorescence assay for anti-SINV IgM. In addition, 31 paired cerebrospinal fluid (CSF) specimens from the same patients were screened for IgM. Micro-neutralization assays were performed on all IgM-positive samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>None of the specimens tested positive for SINV by molecular screening; however, 38\/197 (19.0%) samples were positive for SINV-specific IgM. A total of 25\/38 (65.8%) IgM-positive samples tested positive for SINV-neutralizing antibodies, giving an overall incidence of 12.7%. Furthermore, 2\/31 (6.5%) CSF specimens tested positive for IgM but were negative for neutralizing antibodies. There was a higher incidence of SINV-positive cases in Mpumalanga (26.0%) than Gauteng province (15.0%). The most significant months for IgM-positive cases were April 2019 (OR = 2.9, <jats:italic>p<\/jats:italic> &amp;lt; 0.05), and May 2020 (OR = 7.7, <jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SINV or a closely related virus contributed to 12.7% of AFDUC cases in hospitalized patients during the late summer and autumn months in South Africa and was significantly associated with arthralgia, meningitis, and headaches.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2021.798810","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T06:13:41Z","timestamp":1644214421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Incidence of Sindbis Virus in Hospitalized Patients With Acute Fevers of Unknown Cause in South Africa, 2019\u20132020"],"prefix":"10.3389","volume":"12","author":[{"given":"Kgothatso","family":"Meno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarence","family":"Yah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietjie","family":"Venter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/rmv.1876","article-title":"Sindbis virus as a human pathogen\u2014epidemiology, clinical picture and pathogenesis.","volume":"26","author":"Adouchief","year":"2016","journal-title":"Rev. Med. Virol."},{"key":"B2","author":"Berger","year":"2018","journal-title":"Sindbis Group Viruses: Global Status."},{"key":"B3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1017\/s0950268802007409","article-title":"Epidemiology of Sindbis virus infections in Finland 1981-96: possible factors explaining a peculiar disease pattern.","volume":"129","author":"Brummer-Korvenkontio","year":"2002","journal-title":"Epidemiol. Infect."},{"key":"B4","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/S0140-6736(11)60281-X","article-title":"Chikungunya: a re-emerging virus.","volume":"379","author":"Burt","year":"2012","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1007\/978-1-4612-3900-0_22","article-title":"Togaviridae and Flaviviridae: the alphavirases and flaviviruses","author":"Calisher","year":"1988","journal-title":"Laboratory Diagnosis of Infectious Diseases Principles and Practice"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0171989","DOI":"10.1371\/journal.pone.0171989","article-title":"The neutralizing role of IgM during early Chikungunya virus infection.","volume":"12","author":"Chua","year":"2017","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"561","DOI":"10.4269\/ajtmh.1958.7.561","article-title":"Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses.","volume":"7","author":"Clarke","year":"1958","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.4269\/ajtmh.1984.33.1203","article-title":"Ockelbo disease in Sweden: epidemiological, clinical, and virological data from the 1982 outbreak.","volume":"33","author":"Espmark","year":"1984","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e00915","DOI":"10.1128\/mSphere.00915-19","article-title":"Robustness of serologic investigations for Chikungunya and Mayaro viruses following coemergence.","volume":"5","author":"Fischer","year":"2020","journal-title":"mSphere"},{"key":"B10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.7774\/cevr.2014.3.1.58","article-title":"Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses.","volume":"3","author":"Go","year":"2014","journal-title":"Clin. Exp. Vaccine Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e0006642","DOI":"10.1371\/journal.pntd.0006642","article-title":"Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar.","volume":"12","author":"Guillebaud","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3390\/v11010082","article-title":"Establishment of an alphavirus-specific neutralization assay to distinguish infections with different members of the Semliki Forest complex.","volume":"11","author":"Henss","year":"2019","journal-title":"Viruses"},{"key":"B13","first-page":"218","article-title":"Sindbis and West Nile virus infections in the Witwatersrand-Pretoria region.","volume":"70","author":"Jupp","year":"1986","journal-title":"S. Afr. Med. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1086\/313462","article-title":"O\u2019nyong-nyong fever in south-central Uganda, 1996-1997: clinical features and validation of a clinical case definition for surveillance purposes.","volume":"29","author":"Kiwanuka","year":"1999","journal-title":"Clin. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1086\/430007","article-title":"Clinical and laboratory manifestations of Sindbis virus infection: prospective study, Finland, 2002\u20132003.","volume":"191","author":"Kurkela","year":"2005","journal-title":"J. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3201\/eid1401.070510","article-title":"Sindbis virus infection in resident birds, migratory birds, and humans, Finland.","volume":"14","author":"Kurkela","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/j.1365-2796.2004.01413.x","article-title":"Sindbis viruses and other alphaviruses as cause of human arthritic disease.","volume":"256","author":"Laine","year":"2004","journal-title":"J. Int. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1093\/rheumatology\/39.11.1272","article-title":"Prolonged arthritis associated with Sindbis related (Pogosta) virus infection.","volume":"39","author":"Laine","year":"2000","journal-title":"Rheumatology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ijid.2018.11.047","article-title":"Investigation of serological cross-reactivity within the alphavirus genus using IFA biochip mosaics.","volume":"79","author":"Lattwein","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e00620","DOI":"10.1128\/JVI.00620-19","article-title":"Introduction and dispersal of sindbis virus from Central Africa to Europe.","volume":"93","author":"Ling","year":"2019","journal-title":"J. Virol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/s0140-6736(84)90562-2","article-title":"Isolation of Karelian fever agent from Aedes communis mosquitoes.","volume":"2","author":"Lvov","year":"1984","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1089\/vbz.2007.0623","article-title":"Diagnostics of pogosta disease: antigenic properties and evaluation of sindbis virus IgM and IgG enzyme immunoassays.","volume":"8","author":"Manni","year":"2008","journal-title":"Vector Borne Zoonotic Dis."},{"key":"B23","first-page":"295","article-title":"Epidemics of West Nile and Sindbis viruses in South Africa with Culex (Culex) univittatus Theobald as vector.","volume":"72","author":"McIntosh","year":"1976","journal-title":"S. Afr. J. Sci."},{"key":"B24","first-page":"291","article-title":"Illness caused by Sindbus and Wes Nile viruses in South Africa.","volume":"38","author":"Mcintosh","year":"1964","journal-title":"S. Afr. Med. J."},{"key":"B25","article-title":"Sindbis viral infections","author":"Niklasson","year":"1994","journal-title":"Handbook of Zoonoses. CRC Handbook Series in Zoonoses"},{"key":"B26","first-page":"204","article-title":"Mosquito-borne viral infections in Southern Africa: a public health perspective: of the six mosquito-borne viral infections of interest in Southern Africa, four can cause a haemorrhagic state.","volume":"29","author":"Rautenbach","year":"2011","journal-title":"Continuing Med. Educ."},{"key":"B27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.jviromet.2005.05.005","article-title":"A simple method of estimating fifty per cent endpoints.","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/s0140-6736(85)91146-8","article-title":"Human parvovirus-associated arthritis: a clinical and laboratory description.","volume":"325","author":"Reid","year":"1985","journal-title":"Lancet"},{"key":"B29","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1186\/s12879-021-06238-w","article-title":"The African network for improved diagnostics, epidemiology and management of common infectious agents.","volume":"21","author":"Schubert","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1017\/S0950268813000964","article-title":"Human cases of Sindbis fever in South Africa, 2006\u20132010.","volume":"142","author":"Storm","year":"","journal-title":"Epidemiol. Infect."},{"key":"B31","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.ijid.2014.03.1096","article-title":"Epidemiological features of sindbis fever in South Africa.","volume":"21","author":"Storm","year":"","journal-title":"Int. J. Infect. Dis."},{"key":"B32","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The alphaviruses: gene expression, replication, and evolution.","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"844","DOI":"10.4269\/ajtmh.1955.4.844","article-title":"Sindbis virus: a newly recognized arthropod-transmitted virus1.","volume":"4","author":"Taylor","year":"1955","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B34","doi-asserted-by":"publisher","first-page":"171","DOI":"10.4269\/ajtmh.2001.65.171","article-title":"Geographic variation of notified ross river virus infections in queensland, australia, 1985\u20131996.","volume":"65","author":"Tong","year":"2001","journal-title":"Am. Soc. Trop. Med. Hyg."},{"key":"B35","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.3201\/eid2112.150132","article-title":"Sindbis and Middelburg old world alphaviruses associated with disease in horses, South Africa.","volume":"21","author":"Van Niekerk","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.3201\/eid2112.150132","article-title":"Sindbis and Middelburg old world alphaviruses associated with neurologic disease in horses, South Africa.","volume":"21","author":"van Niekerk","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.coviro.2017.11.004","article-title":"Assessing the zoonotic potential of arboviruses of African origin.","volume":"28","author":"Venter","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.jcv.2014.02.001","article-title":"Macroarray assay for differential diagnosis of meningoencephalitis in southern Africa.","volume":"60","author":"Venter","year":"2014","journal-title":"J. Clin. Virol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/b978-0-12-369408-9.00021-4","article-title":"Chapter 21 - alphaviral encephalitides","author":"Weaver","year":"2009","journal-title":"Vaccines for Biodefense and Emerging and Neglected Diseases"},{"key":"B40","article-title":"Alphavirus infections","author":"Weaver","year":"2011","journal-title":"Tropical Infectious Diseases: Principles, Pathogens and Practice E-Book: Principles, Pathogens and Practice"},{"key":"B41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3109\/00313028209069049","article-title":"Sindbis infection in man.","volume":"12","author":"Woodall","year":"1962","journal-title":"East Afr. Virus Res. Inst. Rep."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.798810\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T06:13:46Z","timestamp":1644214426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.798810\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2021.798810"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.798810","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]},"article-number":"798810"}}