Newer
Older
Digital_Repository / Misc / Mass downloads / UTas / 891.html
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN"
"http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
<html>
  <head>
    <title>UTas ePrints - Exposure to infant siblings during early life and risk of multiple sclerosis</title>
    <script type="text/javascript" src="http://eprints.utas.edu.au/javascript/auto.js"><!-- padder --></script>
    <style type="text/css" media="screen">@import url(http://eprints.utas.edu.au/style/auto.css);</style>
    <style type="text/css" media="print">@import url(http://eprints.utas.edu.au/style/print.css);</style>
    <link rel="icon" href="/images/eprints/favicon.ico" type="image/x-icon" />
    <link rel="shortcut icon" href="/images/eprints/favicon.ico" type="image/x-icon" />
    <link rel="Top" href="http://eprints.utas.edu.au/" />
    <link rel="Search" href="http://eprints.utas.edu.au/cgi/search" />
    <meta content="Ponsonby, A-L." name="eprints.creators_name" />
<meta content="van der Mei, I.A.F." name="eprints.creators_name" />
<meta content="Dwyer, T." name="eprints.creators_name" />
<meta content="Blizzard, Leigh" name="eprints.creators_name" />
<meta content="Taylor, B.V." name="eprints.creators_name" />
<meta content="Kemp, A." name="eprints.creators_name" />
<meta content="Simmons, R." name="eprints.creators_name" />
<meta content="Kilpatrick, T." name="eprints.creators_name" />
<meta content="" name="eprints.creators_id" />
<meta content="Ingrid.vanderMei@utas.edu.au" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="" name="eprints.creators_id" />
<meta content="article" name="eprints.type" />
<meta content="2007-04-02" name="eprints.datestamp" />
<meta content="2008-01-08 15:30:00" name="eprints.lastmod" />
<meta content="show" name="eprints.metadata_visibility" />
<meta content="Exposure to infant siblings during early life and risk of multiple sclerosis" name="eprints.title" />
<meta content="pub" name="eprints.ispublished" />
<meta content="321202" name="eprints.subjects" />
<meta content="restricted" name="eprints.full_text_status" />
<meta content="infant sibling, early life, Epstein-Barr virus, multiple sclerosis" name="eprints.keywords" />
<meta content="Context  The 'hygiene hypothesis' has implicated sibship as a marker of  infection load during early life and suggests exposure or re-exposure to infections can influence the developing immune system. Viral infection has been implicated in the pathogenesis of multiple sclerosis (MS).

Objectives To evaluate whether exposure to infant siblings in early life is associated with the risk of MS . To explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. 

Design, setting and patients   Population-based case-control study in Tasmania, Australia from 1999 to 2001 based on 136 cases of MRI-confirmed MS and 272 community controls, matched on sex and year of birth. 

Main Outcome Measure Risk of MS and serum EBV IgG response by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. 

Results Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (Adjusted Odds Ratios: Less than 1 infant-years, 1:00 [reference]; 1 to 3 infant-years, 0.59 [ 95%CI, 0.34-1.02]; 3 to 5 infant-years, 0.47  [ 95%CI, 0.23, 1.02]; 5 or more infant-years, 0.23 [ 95%CI, 0.07, 0.72]; test for trend p = 0.002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least one infant-year contact had a reduced risk of  infectious mononucleosis (AOR 0.44 [ 95% CI, 0.21,0.92]) and a reduced risk of very high composite EBV IgG titres (AOR 0.33 [ 95% CI, 0.11,0.98 ]) compared to other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titre. 

Conclusion  Higher infant sibling exposure in the first six years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.
" name="eprints.abstract" />
<meta content="2005-01-26" name="eprints.date" />
<meta content="published" name="eprints.date_type" />
<meta content="JAMA" name="eprints.publication" />
<meta content="293" name="eprints.volume" />
<meta content="4" name="eprints.number" />
<meta content="463-469" name="eprints.pagerange" />
<meta content="UNSPECIFIED" name="eprints.thesis_type" />
<meta content="TRUE" name="eprints.refereed" />
<meta content="print 0098-7484; online 1538-3598" name="eprints.issn" />
<meta content="1.Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347:911-20.
2.Isager H, Andersen E, Hyllested K. Risk of Multiple Sclerosis inversely associated with birth order position. Acta Neurol Scand 1980; 61:393-396.
3.Visscher BR, Lui K, Sullivan C, Valdiviezo NL, Detels R. Birth Order and Multiple Sclerosis. Acta Neurol Scand 1982; 66:209-215.
4.Zilber N, Kutai-Berman M, Kahana E, Korczyn AD. Multiple Sclerosis and Birth Order. Acta Neurol Scand 1988; 78:313-317.
5.Ascherio A, Munger KL, Lennette ET, Spiegelman D, Hernan MA, Olek MJ et al. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. JAMA 2001; 286:3083-8.
6. Koch-Henriksen N. An epidemiological study of multiple sclerosis. Acta Neurol Scand 1989; 124:S1-S123.
7.Matias-Guiu J, Ferri L, Falip R, Galiano L, Martin R. Birth order in multiple sclerosis: a population-based case-control study in Alcoi, Spain. Neuroepidemiology 1994; 13:129-130.
8.Arvin AM, Koropchak CM, Wittek AE. Immunologic evidence of reinfection with varicella-zoster virus. J Infect Dis 1983; 148:200-205.
9.Adams CL, MacLeod M.K, James Milner-White E, Aitken R, Garside P, DI. S. Complete analysis of the B Cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation. Immunology 2003; 108:1274-87.
10.Amyes E, Hatton C, Montamat-Sicotte D, Gudgeon N, Rickinson AB, McMichael AJ, et al. Characterisation of the CD4+ T cell response to Esptein-Barr virus during primary and persistent infection. The Journal of Experimental Medicine. 2003; 198:903-911.
11.Wedderburn LR, Patel A, Varsani H, Woo P. The developing human immune system: T-cell receptor repertoire of children and young adults shows a wide discrepancy in the frequency of persistent oligoclonal T-cell expansions. Immunology 2001; 102:301-9.
12.Leibowitz U, Antonovsky A, Medalie J, Smith HA, Halpern L, Alter M. Epidemiological study of multiple sclerosis in Israel. J. Neurol. Neurosurg. Psychiat. 1966; 29:60-68.
13.Haahr S, Koch-Henriksen N, Moller-Larsen A, Eriksen LS, Andersen HM.Increased risk of multiple sclerosis after late Epstein-Barr virus infection: a historical prospective study. Mult Scler 1995; 1(2): 73-7.
14. Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A. Multiple Sclerosis and Epstein-Barr Virus. JAMA 2003; 289:1533-1536.
15.Hernan MA, Oleky MJ, Ascherio A. Cigarette smoking and incidence of multiple sclerosis. Am J Epidemiol. 2001 Jul 1;154(1):69-74.

16.  Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A.Vitamin D intake and incidence of mulitple sclerosis Neurology 2004; 62: 60-65.

17. Freedman, D. M., M. Dosemeci,  Alavanja MC.  Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates.  Occup Environ Med 2000. 57(6): 418-21.

18.van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV et al. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 2003; 327:316.

19. Ullrich SE. Photoimmune suppression and photocarcinogenesis. Front Biosci 2002; 7:684-703.

20. Paty DW, Oger JJ, Kastrukoff LF, et al. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 1988; 38:180-5.
21.Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13:227-231.
22.Rubio JP, Bahlo M, Butzkueven H, van Der Mei IA, Sale MM, Dickinson JL et al.Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis. Am J Hum Genet. 2002 May;70(5):1125-37.
23. Gartner BC, Hess RD, Bandt D, Kruse A, Rethwilm A, Roemer K, Mueller-Lantzsch N.
Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays with an immunofluorescence assay as the reference method.. Clin Diagn Lab Immunol.  2003 Jan;10(1):78-82.  
24.Holt PG. A potential vaccine strategy for asthma and allied atopic diseases during early childhood. Lancet. 1994 Aug 13;344(8920):456-8.
25.Knipe DM, Howley PM, editors. Fields Virology. Vol. 2, 4 Ed.  Philadelphia. Lippincott Williams and Wilkins, 2001.
26.Hosmer DW Jr, Lemeshow S. Applied Logistic Regression 2nd Ed.. New York: John Wiley and Sons Inc., 2000:146,243-58.
27.Rothman KJ. Modern Epidemiology. Boston, Massachusetts: Little, Brown and Co., 1986:150
28.Farr TJ, Harnett GB, Pietroboni GR, Bucens MR. The distribution of antibodies to HHV-6 compared with other herpesviruses in young children. Epidemiol Infect 1990; 105:603-7.
29. Dagan R, Fraser D, Handsher R. Acquisition of immunity in mothers of infants administered trivalent oral poliovirus vaccine. Eur J Clin Microbiol Infect Dis.  1994 Dec;13(12):1029-32.  

30.Villoslada P, Juste C, Tintore M, Llorenc V, Codina G, Pozo-Rosich P, et al. The immune response against herpesvirus is more prominent in the early stages of MS. Neurology 2003; 60:1944-1948.
31.Kim BS, Lyman MA, Kang BS, Kang HK, Lee HG, Mohindru M, et al. Pathogenesis of virus-induced immune-mediated demyelination. Immunol Res 2001; 24:121-30.
32.Alotaibi S, Kennedy J, Tellier R, Stephens D, Banwell B. Epstein-Barr virus in pediatric      multiple sclerosis. JAMA. 2004 Apr 21;291(15):1875-9.
33.Aalto SM, Linnavuori K, Peltola H, Vuori E, Weissbrich B, Schubert J, et al. Immunoreactivation of Epstein-Barr virus due to cytomegalovirus primary infection. J Med Virol 1998; 56:189-191.
34. Huang LM, Lee CY, Chang MH, Wang JD, Hsu CY. Primary infections of Epstein-Barr virus, cytomegalovirus and human herpesvirus-6. Arch Dis Child 1993; 68:408-411.
35.Cuomo L, Angeloni A, Zompetta C, Cirone M, Calogero A, Frati L, et al. Human herpesvirus 6 variant A, but not variant B, infects EBV-positive lymphoid cells, activating the latent EBV genome through a BZLF-1-dependent mechanism. AIDS Res Hum Retroviruses 1995; 11:1241-45.
36. Thomas SL, Wheeler JG, Hall AJ. Contacts with varicella or with children and protection against herpes zoster in adults: a case-control study. Lancet 2002; 360:678-82.
37. Savoldo B, Cubbage ML, Durett AG, Goss J, Huls MH, Liu Z,, et al. Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. J Immunol 2002; 168:909-18.

38. Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80:695-705.

39. Olson JK, Eagar TN, Miller SD. Functional activation of myelin-specific T cells by virus-induced molecular mimicry.J Immunol. 2002 Sep 1;169(5):2719-26

40. Hollsberg P, Hansen HJ, Haahr S. Altered CD8+ T cell responses to selected Epstein-Barr virus immunodominant epitopes in patients with multiple sclerosis. Clin Exp Immunol 2003; 132:137-43.
41. Wing K, Lindgren S, Kollberg G, Lundgren A, Harris RA, Rudin A, et al. CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells. Eur J Immunol 2003; 33:579-87.
42. Ebers GC Sadovnick AD Risch NJ on behalf of the Canadian Collaborative Group. A genetic basis for familial aggregation in multiple sclerosis. Nature 1995; 377:105-6.

" name="eprints.referencetext" />
<meta content="Ponsonby, A-L. and van der Mei, I.A.F. and Dwyer, T. and Blizzard, Leigh and Taylor, B.V. and Kemp, A. and Simmons, R. and Kilpatrick, T. (2005) Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA, 293 (4). pp. 463-469. ISSN print 0098-7484; online 1538-3598" name="eprints.citation" />
<meta content="http://eprints.utas.edu.au/891/1/Ponsonby_JAMA_05.pdf" name="eprints.document_url" />
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" />
<meta content="Exposure to infant siblings during early life and risk of multiple sclerosis" name="DC.title" />
<meta content="Ponsonby, A-L." name="DC.creator" />
<meta content="van der Mei, I.A.F." name="DC.creator" />
<meta content="Dwyer, T." name="DC.creator" />
<meta content="Blizzard, Leigh" name="DC.creator" />
<meta content="Taylor, B.V." name="DC.creator" />
<meta content="Kemp, A." name="DC.creator" />
<meta content="Simmons, R." name="DC.creator" />
<meta content="Kilpatrick, T." name="DC.creator" />
<meta content="321202 Epidemiology" name="DC.subject" />
<meta content="Context  The 'hygiene hypothesis' has implicated sibship as a marker of  infection load during early life and suggests exposure or re-exposure to infections can influence the developing immune system. Viral infection has been implicated in the pathogenesis of multiple sclerosis (MS).

Objectives To evaluate whether exposure to infant siblings in early life is associated with the risk of MS . To explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. 

Design, setting and patients   Population-based case-control study in Tasmania, Australia from 1999 to 2001 based on 136 cases of MRI-confirmed MS and 272 community controls, matched on sex and year of birth. 

Main Outcome Measure Risk of MS and serum EBV IgG response by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. 

Results Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (Adjusted Odds Ratios: Less than 1 infant-years, 1:00 [reference]; 1 to 3 infant-years, 0.59 [ 95%CI, 0.34-1.02]; 3 to 5 infant-years, 0.47  [ 95%CI, 0.23, 1.02]; 5 or more infant-years, 0.23 [ 95%CI, 0.07, 0.72]; test for trend p = 0.002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least one infant-year contact had a reduced risk of  infectious mononucleosis (AOR 0.44 [ 95% CI, 0.21,0.92]) and a reduced risk of very high composite EBV IgG titres (AOR 0.33 [ 95% CI, 0.11,0.98 ]) compared to other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titre. 

Conclusion  Higher infant sibling exposure in the first six years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.
" name="DC.description" />
<meta content="2005-01-26" name="DC.date" />
<meta content="Article" name="DC.type" />
<meta content="PeerReviewed" name="DC.type" />
<meta content="application/pdf" name="DC.format" />
<meta content="http://eprints.utas.edu.au/891/1/Ponsonby_JAMA_05.pdf" name="DC.identifier" />
<meta content="Ponsonby, A-L. and van der Mei, I.A.F. and Dwyer, T. and Blizzard, Leigh and Taylor, B.V. and Kemp, A. and Simmons, R. and Kilpatrick, T. (2005) Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA, 293 (4). pp. 463-469. ISSN print 0098-7484; online 1538-3598" name="DC.identifier" />
<meta content="http://eprints.utas.edu.au/891/" name="DC.relation" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/BibTeX/epprod-eprint-891.bib" title="BibTeX" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/ContextObject/epprod-eprint-891.xml" title="OpenURL ContextObject" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/ContextObject::Dissertation/epprod-eprint-891.xml" title="OpenURL Dissertation" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/ContextObject::Journal/epprod-eprint-891.xml" title="OpenURL Journal" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/DC/epprod-eprint-891.txt" title="Dublin Core" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/DIDL/epprod-eprint-891.xml" title="DIDL" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/EndNote/epprod-eprint-891.enw" title="EndNote" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/HTML/epprod-eprint-891.html" title="HTML Citation" type="text/html; charset=utf-8" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/METS/epprod-eprint-891.xml" title="METS" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/MODS/epprod-eprint-891.xml" title="MODS" type="text/xml" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/RIS/epprod-eprint-891.ris" title="Reference Manager" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/Refer/epprod-eprint-891.refer" title="Refer" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/Simple/epprod-eprint-891text" title="Simple Metadata" type="text/plain" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/Text/epprod-eprint-891.txt" title="ASCII Citation" type="text/plain; charset=utf-8" />
<link rel="alternate" href="http://eprints.utas.edu.au/cgi/export/891/XML/epprod-eprint-891.xml" title="EP3 XML" type="text/xml" />

  </head>
  <body bgcolor="#ffffff" text="#000000" onLoad="loadRoutine(); MM_preloadImages('images/eprints/ePrints_banner_r5_c5_f2.gif','images/eprints/ePrints_banner_r5_c7_f2.gif','images/eprints/ePrints_banner_r5_c8_f2.gif','images/eprints/ePrints_banner_r5_c9_f2.gif','images/eprints/ePrints_banner_r5_c10_f2.gif','images/eprints/ePrints_banner_r5_c11_f2.gif','images/eprints/ePrints_banner_r6_c4_f2.gif')">
    
    <div class="ep_noprint"><noscript><style type="text/css">@import url(http://eprints.utas.edu.au/style/nojs.css);</style></noscript></div>




<table width="795" border="0" cellspacing="0" cellpadding="0">
  <tr>
    <td><script language="JavaScript1.2">mmLoadMenus();</script>
      <table border="0" cellpadding="0" cellspacing="0" width="795">
        <!-- fwtable fwsrc="eprints_banner_final2.png" fwbase="ePrints_banner.gif" fwstyle="Dreamweaver" fwdocid = "1249563342" fwnested="0" -->
        <tr>
          <td><img src="/images/eprints/spacer.gif" width="32" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="104" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="44" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="105" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="41" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="16" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="68" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="68" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="68" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="82" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="69" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="98" height="1" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="1" border="0" alt="" /></td>
        </tr>
        <tr>
          <td colspan="12"><img name="ePrints_banner_r1_c1" src="/images/eprints/ePrints_banner_r1_c1.gif" width="795" height="10" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="10" border="0" alt="" /></td>
        </tr>
        <tr>
          <td rowspan="6"><img name="ePrints_banner_r2_c1" src="/images/eprints/ePrints_banner_r2_c1.gif" width="32" height="118" border="0" alt="" /></td>
          <td rowspan="5"><a href="http://www.utas.edu.au/"><img name="ePrints_banner_r2_c2" src="/images/eprints/ePrints_banner_r2_c2.gif" width="104" height="103" border="0" alt="" /></a></td>
          <td colspan="10"><img name="ePrints_banner_r2_c3" src="/images/eprints/ePrints_banner_r2_c3.gif" width="659" height="41" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="41" border="0" alt="" /></td>
        </tr>
        <tr>
          <td colspan="3"><a href="http://eprints.utas.edu.au/"><img name="ePrints_banner_r3_c3" src="/images/eprints/ePrints_banner_r3_c3.gif" width="190" height="31" border="0" alt="" /></a></td>
          <td rowspan="2" colspan="7"><img name="ePrints_banner_r3_c6" src="/images/eprints/ePrints_banner_r3_c6.gif" width="469" height="37" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="31" border="0" alt="" /></td>
        </tr>
        <tr>
          <td colspan="3"><img name="ePrints_banner_r4_c3" src="/images/eprints/ePrints_banner_r4_c3.gif" width="190" height="6" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="6" border="0" alt="" /></td>
        </tr>
        <tr>
          <td colspan="2"><img name="ePrints_banner_r5_c3" src="/images/eprints/ePrints_banner_r5_c3.gif" width="149" height="1" border="0" alt="" /></td>
          <td rowspan="2" colspan="2"><a href="/information.html" onMouseOut="MM_swapImgRestore();MM_startTimeout()" onMouseOver="MM_showMenu(window.mm_menu_0821132634_0,0,25,null,'ePrints_banner_r5_c5');MM_swapImage('ePrints_banner_r5_c5','','/images/eprints/ePrints_banner_r5_c5_f2.gif',1);"><img name="ePrints_banner_r5_c5" src="/images/eprints/ePrints_banner_r5_c5.gif" width="57" height="25" border="0" alt="About" /></a></td>
          <td rowspan="2"><a href="/view/" onMouseOut="MM_swapImgRestore();MM_startTimeout()" onMouseOver="MM_showMenu(window.mm_menu_0821133021_1,0,25,null,'ePrints_banner_r5_c7');MM_swapImage('ePrints_banner_r5_c7','','/images/eprints/ePrints_banner_r5_c7_f2.gif',1);"><img name="ePrints_banner_r5_c7" src="/images/eprints/ePrints_banner_r5_c7.gif" width="68" height="25" border="0" alt="Browse" /></a></td>
          <td rowspan="2"><a href="/perl/search/simple" onMouseOut="MM_swapImgRestore();MM_startTimeout()" onMouseOver="MM_showMenu(window.mm_menu_0821133201_2,0,25,null,'ePrints_banner_r5_c8');MM_swapImage('ePrints_banner_r5_c8','','/images/eprints/ePrints_banner_r5_c8_f2.gif',1);"><img name="ePrints_banner_r5_c8" src="/images/eprints/ePrints_banner_r5_c8.gif" width="68" height="25" border="0" alt="Search" /></a></td>
          <td rowspan="2"><a href="/perl/register" onMouseOut="MM_swapImgRestore();MM_startTimeout();" onMouseOver="MM_showMenu(window.mm_menu_1018171924_3,0,25,null,'ePrints_banner_r5_c9');MM_swapImage('ePrints_banner_r5_c9','','/images/eprints/ePrints_banner_r5_c9_f2.gif',1);"><img name="ePrints_banner_r5_c9" src="/images/eprints/ePrints_banner_r5_c9.gif" width="68" height="25" border="0" alt="register" /></a></td>
          <td rowspan="2"><a href="/perl/users/home" onMouseOut="MM_swapImgRestore();MM_startTimeout()" onMouseOver="MM_showMenu(window.mm_menu_0821133422_4,0,25,null,'ePrints_banner_r5_c10');MM_swapImage('ePrints_banner_r5_c10','','/images/eprints/ePrints_banner_r5_c10_f2.gif',1);"><img name="ePrints_banner_r5_c10" src="/images/eprints/ePrints_banner_r5_c10.gif" width="82" height="25" border="0" alt="user area" /></a></td>
          <td rowspan="2"><a href="/help/" onMouseOut="MM_swapImgRestore();MM_startTimeout()" onMouseOver="MM_showMenu(window.mm_menu_0821133514_5,0,25,null,'ePrints_banner_r5_c11');MM_swapImage('ePrints_banner_r5_c11','','/images/eprints/ePrints_banner_r5_c11_f2.gif',1);"><img name="ePrints_banner_r5_c11" src="/images/eprints/ePrints_banner_r5_c11.gif" width="69" height="25" border="0" alt="Help" /></a></td>
          <td rowspan="3" colspan="4"><img name="ePrints_banner_r5_c12" src="/images/eprints/ePrints_banner_r5_c12.gif" width="98" height="40" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="1" border="0" alt="" /></td>
        </tr>
        <tr>
          <td rowspan="2"><img name="ePrints_banner_r6_c3" src="/images/eprints/ePrints_banner_r6_c3.gif" width="44" height="39" border="0" alt="ePrints home" /></td>
          <td><a href="/" onMouseOut="MM_swapImgRestore()" onMouseOver="MM_swapImage('ePrints_banner_r6_c4','','/images/eprints/ePrints_banner_r6_c4_f2.gif',1);"><img name="ePrints_banner_r6_c4" src="/images/eprints/ePrints_banner_r6_c4.gif" width="105" height="24" border="0" alt="ePrints home" /></a></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="24" border="0" alt="" /></td>
        </tr>
        <tr>
          <td><img name="ePrints_banner_r7_c2" src="/images/eprints/ePrints_banner_r7_c2.gif" width="104" height="15" border="0" alt="" /></td>
          <td colspan="8"><img name="ePrints_banner_r7_c4" src="/images/eprints/ePrints_banner_r7_c4.gif" width="517" height="15" border="0" alt="" /></td>
          <td><img src="/images/eprints/spacer.gif" width="1" height="15" border="0" alt="" /></td>
        </tr>
      </table></td>
  </tr>
    <tr><td><table width="100%" style="font-size: 90%; border: solid 1px #ccc; padding: 3px"><tr>
      <td align="left"><a href="http://eprints.utas.edu.au/cgi/users/home">Login</a> | <a href="http://eprints.utas.edu.au/cgi/register">Create Account</a></td>
      <td align="right" style="white-space: nowrap">
        <form method="get" accept-charset="utf-8" action="http://eprints.utas.edu.au/cgi/search" style="display:inline">
          <input class="ep_tm_searchbarbox" size="20" type="text" name="q" />
          <input class="ep_tm_searchbarbutton" value="Search" type="submit" name="_action_search" />
          <input type="hidden" name="_order" value="bytitle" />
          <input type="hidden" name="basic_srchtype" value="ALL" />
          <input type="hidden" name="_satisfyall" value="ALL" />
        </form>
      </td>
    </tr></table></td></tr>
  <tr>
    <td class="toplinks"><!-- InstanceBeginEditable name="content" -->


<div align="center">
  
  <table width="720" class="ep_tm_main"><tr><td align="left">
    <h1 class="ep_tm_pagetitle">Exposure to infant siblings during early life and risk of multiple sclerosis</h1>
    <p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Ponsonby, A-L.</span> and <span class="person_name">van der Mei, I.A.F.</span> and <span class="person_name">Dwyer, T.</span> and <span class="person_name">Blizzard, Leigh</span> and <span class="person_name">Taylor, B.V.</span> and <span class="person_name">Kemp, A.</span> and <span class="person_name">Simmons, R.</span> and <span class="person_name">Kilpatrick, T.</span> (2005) <xhtml:em>Exposure to infant siblings during early life and risk of multiple sclerosis.</xhtml:em> JAMA, 293 (4). pp. 463-469. ISSN print 0098-7484; online 1538-3598</p><p style="margin-bottom: 1em" class="not_ep_block"></p><table style="margin-bottom: 1em" class="not_ep_block"><tr><td valign="top" style="text-align:center"><a href="http://eprints.utas.edu.au/891/1/Ponsonby_JAMA_05.pdf"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a></td><td valign="top"><a href="http://eprints.utas.edu.au/891/1/Ponsonby_JAMA_05.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />120Kb</td><td><form method="get" accept-charset="utf-8" action="http://eprints.utas.edu.au/cgi/request_doc"><input accept-charset="utf-8" value="897" name="docid" type="hidden" /><div class=""><input value="Request a copy" name="_action_null" class="ep_form_action_button" onclick="return EPJS_button_pushed( '_action_null' )" type="submit" /> </div></form></td></tr></table><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">Context  The 'hygiene hypothesis' has implicated sibship as a marker of  infection load during early life and suggests exposure or re-exposure to infections can influence the developing immune system. Viral infection has been implicated in the pathogenesis of multiple sclerosis (MS).&#13;
&#13;
Objectives To evaluate whether exposure to infant siblings in early life is associated with the risk of MS . To explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. &#13;
&#13;
Design, setting and patients   Population-based case-control study in Tasmania, Australia from 1999 to 2001 based on 136 cases of MRI-confirmed MS and 272 community controls, matched on sex and year of birth. &#13;
&#13;
Main Outcome Measure Risk of MS and serum EBV IgG response by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. &#13;
&#13;
Results Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (Adjusted Odds Ratios: Less than 1 infant-years, 1:00 [reference]; 1 to 3 infant-years, 0.59 [ 95%CI, 0.34-1.02]; 3 to 5 infant-years, 0.47  [ 95%CI, 0.23, 1.02]; 5 or more infant-years, 0.23 [ 95%CI, 0.07, 0.72]; test for trend p = 0.002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least one infant-year contact had a reduced risk of  infectious mononucleosis (AOR 0.44 [ 95% CI, 0.21,0.92]) and a reduced risk of very high composite EBV IgG titres (AOR 0.33 [ 95% CI, 0.11,0.98 ]) compared to other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titre. &#13;
&#13;
Conclusion  Higher infant sibling exposure in the first six years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.&#13;
</p></div><table style="margin-bottom: 1em" cellpadding="3" class="not_ep_block" border="0"><tr><th valign="top" class="ep_row">Item Type:</th><td valign="top" class="ep_row">Article</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">infant sibling, early life, Epstein-Barr virus, multiple sclerosis</td></tr><tr><th valign="top" class="ep_row">Subjects:</th><td valign="top" class="ep_row"><a href="http://eprints.utas.edu.au/view/subjects/321202.html">320000 Medical and Health Sciences &gt; 321200 Public Health and Health Services &gt; 321202 Epidemiology</a></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">891</td></tr><tr><th valign="top" class="ep_row">Deposited By:</th><td valign="top" class="ep_row"><span class="ep_name_citation"><span class="person_name">Dr Ingrid A F van der Mei</span></span></td></tr><tr><th valign="top" class="ep_row">Deposited On:</th><td valign="top" class="ep_row">02 Apr 2007</td></tr><tr><th valign="top" class="ep_row">Last Modified:</th><td valign="top" class="ep_row">09 Jan 2008 02:30</td></tr><tr><th valign="top" class="ep_row">ePrint Statistics:</th><td valign="top" class="ep_row"><a target="ePrintStats" href="/es/index.php?action=show_detail_eprint;id=891;">View statistics for this ePrint</a></td></tr></table><p align="right">Repository Staff Only: <a href="http://eprints.utas.edu.au/cgi/users/home?screen=EPrint::View&amp;eprintid=891">item control page</a></p>
  </td></tr></table>
</div>



    <!-- InstanceEndEditable --></td>
  </tr>
  <tr>
    <td><!-- #BeginLibraryItem "/Library/footer_eprints.lbi" -->
    <table width="795" border="0" align="left" cellpadding="0" class="footer">
  <tr valign="top">
<td colspan="2"><div align="center"><a href="http://www.utas.edu.au">UTAS home</a> | <a href="http://www.utas.edu.au/library/">Library home</a> | <a href="/">ePrints home</a> | <a href="/contact.html">contact</a> | <a href="/information.html">about</a> | <a href="/view/">browse</a> | <a href="/perl/search/simple">search</a> | <a href="/perl/register">register</a> | <a href="/perl/users/home">user area</a> | <a href="/help/">help</a></div><br /></td>
</tr>
<tr><td colspan="2"><p><img src="/images/eprints/footerline.gif" width="100%" height="4" /></p></td></tr>
      <tr valign="top">
        <td width="68%" class="footer">Authorised by the University Librarian<br />
© University of Tasmania ABN 30 764 374 782<br />
      <a href="http://www.utas.edu.au/cricos/">CRICOS Provider Code 00586B</a> | <a href="http://www.utas.edu.au/copyright/copyright_disclaimers.html">Copyright &amp; Disclaimers</a> | <a href="http://www.utas.edu.au/accessibility/index.html">Accessibility</a> | <a href="http://eprints.utas.edu.au/feedback/">Site Feedback</a>  </td>
        <td width="32%"><div align="right">
            <p align="right" class="NoPrint"><a href="http://www.utas.edu.au/"><img src="http://www.utas.edu.au/shared/logos/unioftasstrip.gif" alt="University of Tasmania Home Page" width="260" height="16" border="0" align="right" /></a></p>
            <p align="right" class="NoPrint"><a href="http://www.utas.edu.au/"><br />
            </a></p>
        </div></td>
      </tr>
      <tr valign="top">
        <td><p>  </p></td>
        <td><div align="right"><span class="NoPrint"><a href="http://www.eprints.org/software/"><img src="/images/eprintslogo.gif" alt="ePrints logo" width="77" height="29" border="0" align="bottom" /></a></span></div></td>
      </tr>
    </table>
    <!-- #EndLibraryItem -->
    <div align="center"></div></td>
  </tr>
</table>

  </body>
</html>