{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T19:59:46Z","timestamp":1777751986738,"version":"3.51.4"},"reference-count":47,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2013,5,24]]},"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To quantify a range of haematological indicators of viral infection (leucocyte apoptosis, cytopenia of normal lymphocytes, reactive lymphocyte increase, neutropenia) in patients with recent onset invasive meningococcal disease (IMD), with a view to test the association of viral infection with IMD and identify possible haematological risk factors for its development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects and methods<\/jats:title>\n                  <jats:p>88 patients with recent onset IMD, classified on clinical severity as fatal (n=14), septic shock survived (n=26) and no shock (n=48), and 50 healthy controls were studied. Blood film microscopy and leucocyte counts were used to quantify the virus-associated indicators. Cocci-containing neutrophils were also quantified.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All viral parameters were significantly more frequent or higher in patients than controls, with leucocyte apoptosis found only in the patients. A significant gradient in accord with clinical severity was found for neutrophil and lymphocyte apoptosis, neutropenia and cocci-containing neutrophils. Crucially, apoptotic neutrophils did not contain cocci, and cocci-containing neutrophils were not apoptotic.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The correlation between magnitude of neutrophil apoptosis and severity of IMD suggests a cause\u2013effect relationship. We propose that neutrophil apoptosis is more likely a facilitator rather than an effect of IMD for these reasons: (1) apoptotic neutrophils did not contain cocci and cocci-containing neutrophils were not apoptotic, (2) leucocyte apoptosis is a recognised viral effect and (3) <jats:italic>Neisseria meningitidis<\/jats:italic> is incapable of producing a Panton\u2013Valentine type leucocidin. The lymphocyte apoptosis which accompanies neutrophil death may contribute to risk by impairing the generation of microbicidal antibody. Leucocyte apoptosis is a morphological expression of viral immunosuppression and, we suggest, is a likely contributor to a range of viral effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2013-201579","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T21:09:14Z","timestamp":1372194554000},"page":"976-981","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease"],"prefix":"10.1136","volume":"66","author":[{"given":"Harry","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Queensland, Royal Children's Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon L","family":"Rogers","sequence":"additional","affiliation":[{"name":"Division of Haematology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen V","family":"Smith","sequence":"additional","affiliation":[{"name":"Public Health Microbiology, Communicable Disease, Forensic and Scientific Services, Queensland Health, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gillis","sequence":"additional","affiliation":[{"name":"Division of Immunology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Siskind","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Queensland, Royal Children's Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2013,6,25]]},"reference":[{"key":"2025092503442322000_66.11.976.1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91112-8"},{"key":"2025092503442322000_66.11.976.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03450100061026"},{"key":"2025092503442322000_66.11.976.3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1017\/S0950268801005696","article-title":"Risk-factors for meningococcal disease in Victoria, Australia in 1997","volume":"127","author":"Robinson","year":"2001","journal-title":"Epidemiol Infect"},{"key":"2025092503442322000_66.11.976.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2004.00564.x"},{"key":"2025092503442322000_66.11.976.5","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyi295"},{"key":"2025092503442322000_66.11.976.6","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1301-1309.2002"},{"key":"2025092503442322000_66.11.976.7","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00481-09"},{"key":"2025092503442322000_66.11.976.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)08350-0"},{"key":"2025092503442322000_66.11.976.9","doi-asserted-by":"publisher","DOI":"10.1086\/379324"},{"key":"2025092503442322000_66.11.976.10","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.molimm.2005.06.025","article-title":"Complement deficiency and disease: an update","volume":"43","author":"Sj\u00f6holm","year":"2005","journal-title":"Mol Immunol"},{"key":"2025092503442322000_66.11.976.11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1017\/S095026880006828X","article-title":"Effect of respiratory syncytial virus infection on binding of Neisseria meningitidis and Haemophilus influenzae type b to a human epithelial cell line (HEp-2)","volume":"110","author":"Raza","year":"1993","journal-title":"Epidemiol Infect"},{"key":"2025092503442322000_66.11.976.12","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21623"},{"key":"2025092503442322000_66.11.976.13","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00155-09"},{"key":"2025092503442322000_66.11.976.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000405"},{"key":"2025092503442322000_66.11.976.15","doi-asserted-by":"crossref","unstructured":"Bain B . Blood cells. A practical guide. Oxford: Blackwell Publishing, 2006:204, pp. 400\u201306.","DOI":"10.1002\/9780470987551"},{"key":"2025092503442322000_66.11.976.16","unstructured":"Smith H . A morphological study of histiocytes and phagocytic mononuclear cells in human peripheral blood . MD thesis, Univ of Melbourne, 1966."},{"key":"2025092503442322000_66.11.976.17","unstructured":"Smith H . Diagnosis in paediatric haematology. Edinburgh: Churchill Livingstone, 1996:8, pp. 239\u201371."},{"key":"2025092503442322000_66.11.976.18","first-page":"951","article-title":"Peripheral blood lymphocyte apoptosis. A clue to the diagnosis of acute infectious mononucleosis","volume":"120","author":"Fischer","year":"1996","journal-title":"Arch Pathol Lab Med"},{"key":"2025092503442322000_66.11.976.19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2257.1999.00219.x"},{"key":"2025092503442322000_66.11.976.20","first-page":"56","article-title":"Leucocyte death in generalized virus infection","volume":"5","author":"Smith","year":"1969","journal-title":"The Australian Paed J"},{"key":"2025092503442322000_66.11.976.21","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5694\/j.1326-5377.1964.tb115672.x","article-title":"The prevalence and diagnostic significance of \u201chistiocytes\u201d and phagocytic mononuclear cells in peripheral blood films","volume":"2","author":"Smith","year":"1964","journal-title":"Med J Aust"},{"key":"2025092503442322000_66.11.976.22","first-page":"329","article-title":"Cellular expressions and serum concentrations of Fas ligand and Fas receptor in patients with infectious mononucleosis","volume":"72","author":"Sato","year":"2000","journal-title":"Int J Hematol"},{"key":"2025092503442322000_66.11.976.23","first-page":"61","article-title":"T lymphocytes in infectious mononucleosis. I. T cell death in vitro","volume":"60","author":"Moss","year":"1985","journal-title":"Clin Exp Immunol"},{"key":"2025092503442322000_66.11.976.24","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1182\/blood.V80.2.452.452","article-title":"Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein Barr virus-induced infectious mononucleosis","volume":"80","author":"Uehara","year":"1992","journal-title":"Blood"},{"key":"2025092503442322000_66.11.976.25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10590"},{"key":"2025092503442322000_66.11.976.26","unstructured":"Dacie JV Lewis SM . Practical haematology. 7th edn. London: Churchill Livingstone, 1991:4."},{"key":"2025092503442322000_66.11.976.27","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2713"},{"key":"2025092503442322000_66.11.976.28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22684"},{"key":"2025092503442322000_66.11.976.29","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.1.144-166.2000"},{"key":"2025092503442322000_66.11.976.30","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R"},{"key":"2025092503442322000_66.11.976.31","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000191816.57544.b4"},{"key":"2025092503442322000_66.11.976.32","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1182\/blood.V93.7.2395","article-title":"Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria","volume":"93","author":"Colamussi","year":"1999","journal-title":"Blood"},{"key":"2025092503442322000_66.11.976.33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1182\/blood.V92.1.291.413k34_291_299","article-title":"Epstein-Barr virus infects and induces apoptosis in human neutrophils","volume":"92","author":"Larochelle","year":"1998","journal-title":"Blood"},{"key":"2025092503442322000_66.11.976.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2006.02.008"},{"key":"2025092503442322000_66.11.976.35","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21078"},{"key":"2025092503442322000_66.11.976.36","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.1128\/JVI.73.13.5921-5929.2001","article-title":"Human lymphocyte apoptosis after exposure to influenza-A virus","volume":"73","author":"Nichols","year":"2001","journal-title":"J Virol"},{"key":"2025092503442322000_66.11.976.37","first-page":"3171","article-title":"In situ RT-PCR detection of Epstein-Barr Virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes","volume":"18","author":"Guan","year":"1998","journal-title":"Anticancer Res"},{"key":"2025092503442322000_66.11.976.38","first-page":"70","article-title":"T lymphocytes in infectious mononucleosis. II. Response in vitro to interleukin-2 and establishment of T-cell lines","volume":"60","author":"Bishop","year":"1985","journal-title":"Clin Exp Immunol"},{"key":"2025092503442322000_66.11.976.39","first-page":"34","article-title":"T cell cytokine profile during primary Epstein-Barr virus infection (infectious mononucleosis)","volume":"14","author":"Attarbaschi","year":"2003","journal-title":"Eur Cytokine Netw"},{"key":"2025092503442322000_66.11.976.40","first-page":"263","article-title":"High TH1-tpye cytokine serum levels in patients with infectious mononucleosis","volume":"48","author":"Corsi","year":"2004","journal-title":"Acta Virol"},{"key":"2025092503442322000_66.11.976.41","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0117-0"},{"key":"2025092503442322000_66.11.976.42","doi-asserted-by":"publisher","DOI":"10.1080\/003655402753395229"},{"key":"2025092503442322000_66.11.976.43","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-198705000-00007"},{"key":"2025092503442322000_66.11.976.44","doi-asserted-by":"publisher","DOI":"10.1007\/s007050050683"},{"key":"2025092503442322000_66.11.976.45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0140-6736(73)93265-0","article-title":"Tuberculin anergy and infectious mononucleosis","volume":"2","author":"Haider","year":"1973","journal-title":"Lancet"},{"key":"2025092503442322000_66.11.976.46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1365-2141.1995.tb08912.x","article-title":"Increased levels of soluble CD8 and CD4 in patients with infectious mononucleosis","volume":"89","author":"Yoneyama","year":"1995","journal-title":"Br J Haematol"},{"key":"2025092503442322000_66.11.976.47","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.638"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jclinpath-2013-201579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T10:44:36Z","timestamp":1758797076000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2013-201579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,25]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,10,31]]},"published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1136\/jclinpath-2013-201579"],"URL":"https:\/\/doi.org\/10.1136\/jclinpath-2013-201579","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,25]]}}}