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Dtsch Med Wochenschr 2015; 140(18): 1385-1390
DOI: 10.1055/s-0041-104246
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© Georg Thieme Verlag KG Stuttgart · New York

Geschlechtsunterschiede bei Infektionserkrankungen

Sex differences in infectious diseases and their clinical consequences
Claudia Beisel
1   I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
2   Deutsches Zentrum für Infektionsforschung (DZIF) Standort Hamburg – Lübeck – Borstel
3   Heinrich-Pette-Institut, Leibniz Institut für Experimentelle Virologie, Hamburg
,
Jan van Lunzen
1   I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
2   Deutsches Zentrum für Infektionsforschung (DZIF) Standort Hamburg – Lübeck – Borstel
3   Heinrich-Pette-Institut, Leibniz Institut für Experimentelle Virologie, Hamburg
4   Ambulanzzentrum Infektiologie, Universitätsklinikum Hamburg-Eppendorf
,
Ansgar W. Lohse
1   I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
2   Deutsches Zentrum für Infektionsforschung (DZIF) Standort Hamburg – Lübeck – Borstel
,
Marylyn M. Addo
1   I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
2   Deutsches Zentrum für Infektionsforschung (DZIF) Standort Hamburg – Lübeck – Borstel
,
Marcus Altfeld
2   Deutsches Zentrum für Infektionsforschung (DZIF) Standort Hamburg – Lübeck – Borstel
3   Heinrich-Pette-Institut, Leibniz Institut für Experimentelle Virologie, Hamburg
5   Ragon Institute of MGH, MIT and Harvard, Cambridge, USA
› Author Affiliations
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Publication History

Publication Date:
11 September 2015 (online)

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Zusammenfassung

Geschlechtsunterschiede bei Empfänglichkeit, Krankheitsverlauf und Therapieansprechen bei Infektionserkrankungen entstehen aufgrund von unterschiedlichen biologische Faktoren, wie Einflüssen verschiedener X-chromosomal-kodierter Gene und hormonell bedingter Faktoren, sowie durch soziokulturelle Faktoren.

Frauen weisen sowohl eine stärkere angeborene als auch eine ausgeprägtere adaptive Immunantwort gegenüber verschiedenen Pathogenen und Impfstoffen auf, was einen Vorteil bei der Bekämpfung von akuten Infektionen darstellt. Aufgrund einer gesteigerten generalisierten Immunaktivierung in chronisch verlaufenden Infektionen, wie beispielsweise der HIV-1-Infektion ist dies jedoch mit einem schnelleren Krankheitsprogress assoziiert. Entscheidend werden Geschlechtsunterschiede von soziokulturellen Verhaltensmustern beeinflusst, welche Unterschiede in der Exposition gegenüber verschiedenen Krankheitserregern mit sich bringen und folglich zu unterschiedlichen Infektionsrisiken zwischen Frauen und Männern führen.

Es ist wichtig soziokulturelle Hintergründe sowie immunologische Mechanismen, welche den Geschlechtsunterschieden bei Infektionskrankheiten zugrunde liegen, besser zu verstehen und weiter zu erforschen. Das ist eine Voraussetzung, um individualisierte und geschlechtsspezifische Behandlungs- und Impfstrategien, welche zu effektiveren Therapien und einer Reduktion von Nebenwirkungen führen können, zu entwickeln. Dies erfordert auch ein ausgeglichenes Verhältnis weiblicher und männlicher Studienteilnehmer sowohl in grundlagenwissenschaftlichen als auch in klinischen Studien [10].

Abstract

Differences between women and men range from their anatomy, their natural social behavior to their susceptibility and response to different pathologies, including infectious diseases.

The underlying mechanisms of sex differences in infectious diseases are manifold, including differences in exposure to common pathogens, genetic factors that modulate immune responses against pathogens and hormonal factors that may alter susceptibility or disease progression, and responsiveness to treatment. On one hand, these mechanisms lead to higher innate and adaptive immune responses in females, which result in faster clearance of acute infections and higher antibody responses to several vaccines, on the other hand this contributes to an increased susceptibility to chronic inflammatory diseases.

In this review we summarize the underlying causes of sex differences in prevalence, clinical course of disease and treatment outcome of infectious diseases. In order to develop individualized treatment concepts, a fair balance between the sexes should be maintained in basic science, preclinical and clinical studies.

Schlüsselwörter

Geschlechtsunterschiede - Infektionskrankheiten - Virale Infektionen

Keywords

Sex differences - infectious diseases - viral infections
 

  • Literatur

  • 1 World Health Organization. Update: WHO-confirmed human cases of avian influenza A (H5N1) infection, November 2003-May 2008. Wkly Epidemiol Rec 2008; 83: 415-420
    PubMedGoogle Scholar
  • 2 World Health Organization. Hepatitis B Fact sheet N°204. 2012. http://www.who.int/mediacentre/factsheets/fs204/en/ Letzter Zugriff am 29.07.15
    Google Scholar
  • 3 Joint United Nations Programme on HIV/AIDS (UNAIDS). Global report UNAIDS report on the global AIDS epidemic 2013. http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Global_Report_2013_en_1.pdf Letzter Zugriff am 17.08.2015
    CrossrefGoogle Scholar
  • 4 Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat Med 2013; 19: 548-556
    PubMedGoogle Scholar
  • 5 Beignon AS, McKenna K, Skoberne M et al. Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 2005; 115: 3265-3275
    CrossrefPubMedGoogle Scholar
  • 6 Berghöfer B, Frommer T, Haley G et al. TLR7 ligands induce higher IFN-alpha production in females. J Immunol 2006; 177: 2088-2096
    CrossrefPubMedGoogle Scholar
  • 7 Butterworth M, McClellan B, Allansmith M. Influence of sex in immunoglobulin levels. Nature 1967; 214: 1224-1225
    CrossrefPubMedGoogle Scholar
  • 8 Choudhry MA, Bland KI, Chaudry IH. Gender and susceptibility to sepsis following trauma. Endocr Metab Immune Disord Drug Targets 2006; 6: 127-135
    CrossrefPubMedGoogle Scholar
  • 9 Chu CM, Sheen IS, Lin SM, Liaw YF. Sex difference in chronic hepatitis B virus infection: studies of serum HBeAg and alanine aminotransferase levels in 10,431 asymptomatic Chinese HBsAg carriers. Clin Infect Dis 1993; 16: 709-713
    CrossrefPubMedGoogle Scholar
  • 10 Clayton JA, Collins FS. Policy: NIH to balance sex in cell and animal studies. Nature 2014; 509: 282-283
    Google Scholar
  • 11 Cook IF. Sex differences in injection site reactions with human vaccines. Hum Vaccin 2009; 5: 441-449
    CrossrefPubMedGoogle Scholar
  • 12 Dawood FS, Iuliano AD, Reed C et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 2012; 12: 687-695
    CrossrefPubMedGoogle Scholar
  • 13 Farzadegan H, Hoover DR, Astemborski J et al. Sex differences in HIV-1 viral load and progression to AIDS. Lancet 1998; 352: 1510-1514
    CrossrefPubMedGoogle Scholar
  • 14 Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 2008; 8: 737-744
    CrossrefPubMedGoogle Scholar
  • 15 Fitch KV, Srinivasa S, Abbara S et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 2013; 208: 1737-1746
    CrossrefPubMedGoogle Scholar
  • 16 Furman D, Hejblum BP, Simon N et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Nat Acad Sci USA 2014; 111: 869-874
    CrossrefPubMedGoogle Scholar
  • 17 Gabriel G, Arck PC. Sex, immunity and influenza. J Infect Dis 2014; 209 (Suppl. 03) S93-S99
    CrossrefPubMedGoogle Scholar
  • 18 Gleicher N, Barad DH. Gender as risk factor for autoimmune diseases. J Autoimmun 2007; 28: 1-6
    CrossrefPubMedGoogle Scholar
  • 19 Gordeeva LA, Shabaldin AV, Semenova EM et al. [Influence of genetic and phenotypical factors on the efficiency of the vaccination of young children against diphtheria and measles]. Zh Mikrobiol Epidemiol Immunobiol 2006; (02) 42-46
    PubMedGoogle Scholar
  • 20 Greenblatt DJ, Harmatz JS, Singh NN et al. Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration. J Clin Pharmacol 2014; 54: 282-290
    CrossrefPubMedGoogle Scholar
  • 21 Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 2013; 10: 553-562
    CrossrefPubMedGoogle Scholar
  • 22 Hardy JM, Azarowicz EN, Mannini A et al. The effect of Asian influenza on the outcome of pregnancy, Baltimore, 1957–1958. Am J Public Health Nations Health 1961; 51: 1182-1188
    CrossrefPubMedGoogle Scholar
  • 23 Heil F, Hemmi H, Hochrein H et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004; 303: 1526-1529
    CrossrefPubMedGoogle Scholar
  • 24 Izzo RA, Cicardo VH. Gonads and experimental tuberculosis. Nature 1947; 159: 155
    PubMedGoogle Scholar
  • 25 Klein SL. Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases. Bioessays 2012; 34: 1050-1059
    CrossrefPubMedGoogle Scholar
  • 26 Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis 2010; 10: 338-349
    CrossrefPubMedGoogle Scholar
  • 27 Lawitz E, Mangia A, Wyles D et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368: 1878-1887
    CrossrefPubMedGoogle Scholar
  • 28 Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol 2010; 10: 594-604
    CrossrefPubMedGoogle Scholar
  • 29 Marriott I, Huet-Hudson YM. Sexual dimorphism in innate immune responses to infectious organisms. Immunol Res 2006; 34: 177-192
    CrossrefPubMedGoogle Scholar
  • 30 Martin GE, Gouillou M, Hearps AC et al. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women. PLoS One 2013; 8: e55279
    CrossrefPubMedGoogle Scholar
  • 31 McHutchison JG, Lawitz EJ, Shiffman ML et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361: 580-593
    CrossrefPubMedGoogle Scholar
  • 32 Meditz AL, MaWhinney S, Allshouse A et al. Sex, race, and geographic region influence clinical outcomes following primary HIV-1 infection. J Infect Dis 2011; 203: 442-451
    CrossrefPubMedGoogle Scholar
  • 33 Meier A, Chang JJ, Chan ES et al. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med 2009; 15: 955-959
    CrossrefPubMedGoogle Scholar
  • 34 Mosca L, Barrett-Connor E, Wenger NK. Sex /gender differences in cardiovascular disease prevention: what a difference a decade makes. Circulation 2011; 124: 2145-2154
    CrossrefPubMedGoogle Scholar
  • 35 Neyrolles O, Quintana-Murci L. Sexual inequality in tuberculosis. PLoS Med 2009; 6: e1000199
    CrossrefPubMedGoogle Scholar
  • 36 Nguyen DC, Masseoud F, Lu X et al. 17beta-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model. Vaccine 2011; 29: 2515-2518
    CrossrefPubMedGoogle Scholar
  • 37 O‘Garra A, Redford PS, McNab FW et al. The immune response in tuberculosis. Annu Rev Immunol 2013; 31: 475-527
    CrossrefPubMedGoogle Scholar
  • 38 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349: 825-832
    CrossrefPubMedGoogle Scholar
  • 39 Robert Koch-Institut. HIV-Infektionen und AIDS-Erkrankungen in Deutschland – Bericht zur Entwicklung im Jahr 2013 aus dem Robert Koch-Institut. Epidemiologisches Bulletin 2014; 215-232
    PubMedGoogle Scholar
  • 40 Serfling RE, Sherman IL, Houseworth WJ. Excess pneumonia-influenza mortality by age and sex in three major influenza A2 epidemics, United States, 1957–58, 1960 and 1963. Am J Epidemiol 1967; 86: 433-441
    PubMedGoogle Scholar
  • 41 Shimizu I. Impact of oestrogens on the progression of liver disease. Liver Int 2003; 23: 63-69
    CrossrefPubMedGoogle Scholar
  • 42 Siston AM, Rasmussen SA, Honein MA et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010; 303: 1517-1525
    CrossrefPubMedGoogle Scholar
  • 43 Stanberry LR, Spruance SL, Cunningham AL et al. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N Engl J Med 2002; 347: 1652-1661
    CrossrefPubMedGoogle Scholar
  • 44 Su FH, Chen JD, Cheng SH et al. Seroprevalence of Hepatitis-B infection amongst Taiwanese university students 18 years following the commencement of a national Hepatitis-B vaccination program. J Med Virol 2007; 79: 138-143
    CrossrefPubMedGoogle Scholar
  • 45 Theng TS, Chan RK. Genital herpes in a sexually-transmitted infection clinic in Singapore: a 1-year retrospective study. Ann Acad Med Singapore 2004; 33: 200-203
    PubMedGoogle Scholar
  • 46 Thomas DL, Thio CL, Martin MP et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009; 461: 798-801
    CrossrefPubMedGoogle Scholar
  • 47 Thürmann PA. Geschlechtsspezifische Unterschiede in der Pharmakokinetik und -dynamik von Arzneimitteln. Bundesgesundheitsblatt Gesundheitsforsch Gesundheitsschutz 2005; 48: 536-540
    PubMedGoogle Scholar
  • 48 Villa E, Karampatou A, Camma C et al. Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C. Gastroenterology 2011; 140: 818-829
    CrossrefPubMedGoogle Scholar
  • 49 Villa E, Vukotic R, Camma C et al. Reproductive status is associated with the severity of fibrosis in women with hepatitis C. PLoS One 2012; 7: e44624
    CrossrefPubMedGoogle Scholar
  • 50 Wald A. Herpes simplex virus type 2 transmission: risk factors and virus shedding. Herpes 2004; 11 (Suppl. 03) 130A-137A
    PubMedGoogle Scholar
  • 51 Wang CC, Krantz E, Klarquist J et al. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J Infect Dis 2007; 196: 1474-1482
    CrossrefPubMedGoogle Scholar
  • 52 World Health Organization. Global Epidemiological Surveillance Standards for Influenza. 2013. http://www.who.int/influenza/resources/documents/WHO_Epidemiological_Influenza_Surveillance_Standards_2014.pdf Letzter Zugriff am 29.07.2015
    Google Scholar
  • 53 Zacharakis GH, Koskinas J, Kotsiou S et al. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II / EC-project). J Med Virol 2005; 77: 173-179
    CrossrefPubMedGoogle Scholar