Current Infectious Disease Reports

, Volume 14, Issue 2, pp 175–184 | Cite as

Herpes Diagnostic Tests and Their Use

Sexually Transmitted Diseases (L Bachmann, Section Editor)


Genital Herpes is common, causes a broad spectrum of clinical disease, and enhances susceptibility to other sexually transmitted infections, including HIV. Accurate diagnosis of Herpes Simplex Virus infection is important in surveillance, diagnosis and management, screening, and quality assurance. We have reviewed currently available herpes diagnostics and their appropriate use.


Herpes HSV-1 HSV-2 NATS ELISA Point-of-care Western blot Serologies HIV Pregnancy 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Seroprevalence of herpes simplex virus type 2 among persons aged 14–49 years—United States, 2005–2008. MMWR Morb Mortal Wkly Rep 2010;59:456–9. This article provides current estimates of the prevalence of HSV-2 in the United States. It demonstrates that HSV-2 seroprovalence has decreased slightly although not signficantly over time. It further characterizes those populations at greatest risk of having HSV-2.Google Scholar
  2. 2.
    Siegal FP, Lopez C, Hammer GS, et al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981;305:1439–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Wauters O, Lebas E, Nikkels AF. Chronic mucocutaneous herpes simplex virus and varicella zoster virus infections. J Am Acad Dermatol 2010.Google Scholar
  4. 4.
    Kleinschmidt-DeMasters BK, Gilden DH. The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol. 2001;11:440–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Corey L, Wald A, et al. Genital Herpes. In: Holmes KK, Sparling PF, Mardh P, editors. Sexually transmitted diseases. New York: McGraw-Hill; 1999.Google Scholar
  6. 6.
    Engelberg R, Carrell D, Krantz E, Corey L, Wald A. Natural history of genital herpes simplex virus type 1 infection. Sex Transm Dis. 2003;30:174–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370:2127–37.PubMedCrossRefGoogle Scholar
  8. 8.
    Horowitz R, Aierstuck S, Williams EA, Melby B. Herpes simplex virus infection in a university health population: clinical manifestations, epidemiology, and implications. J Am Coll Health. 2010;59:69–74.PubMedCrossRefGoogle Scholar
  9. 9.
    Kortekangas-Savolainen O, Vuorinen T. Trends in herpes simplex virus type 1 and 2 infections among patients diagnosed with genital herpes in a Finnish sexually transmitted disease clinic, 1994–2002. Sex Transm Dis. 2007;34:37–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Ribes JA, Steele AD, Seabolt JP, Baker DJ. Six-year study of the incidence of herpes in genital and nongenital cultures in a central Kentucky medical center patient population. J Clin Microbiol. 2001;39:3321–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Tran T, Druce JD, Catton MC, Kelly H, Birch CJ. Changing epidemiology of genital herpes simplex virus infection in Melbourne, Australia, between 1980 and 2003. Sex Transm Infect. 2004;80:277–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Merin A, Pachankis JE. The psychological impact of genital herpes stigma. J Health Psychol. 2011;16:80–90.PubMedCrossRefGoogle Scholar
  13. 13.
    Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001;357:1149–53.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhu J, Hladik F, Woodward A, et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009;15:886–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhu J, Koelle DM, Cao J, et al. Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation. J Exp Med. 2007;204:595–603.PubMedCrossRefGoogle Scholar
  16. 16.
    Langenberg AG, Corey L, Ashley RL, Leong WP, Straus SE. A prospective study of new infections with herpes simplex virus type 1 and type 2. Chiron HSV Vaccine Study Group. N Engl J Med. 1999;341:1432–8.PubMedCrossRefGoogle Scholar
  17. 17.
    •• Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59:1–110. Provides current recommendations for GH testing and treatment.PubMedGoogle Scholar
  18. 18.
    Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337:1105–11.PubMedCrossRefGoogle Scholar
  19. 19.
    Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296:964–73.PubMedCrossRefGoogle Scholar
  20. 20.
    Pouget ER, Kershaw TS, Blankenship KM, Ickovics JR, Niccolai LM. Racial/ethnic disparities in undiagnosed infection with herpes simplex virus type 2. Sex Transm Dis. 2010;37:538–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Pratt LA, Xu F, McQuillan GM, Robitz R. The association of depression, risky sexual behaviours and herpes simplex virus type 2 in adults in NHANES, 2005–2008. Sex Transm Infect. 2011.Google Scholar
  22. 22.
    Xu F, Sternberg MR, Markowitz LE. Men who have sex with men in the United States: demographic and behavioral characteristics and prevalence of HIV and HSV-2 infection: results from National Health and Nutrition Examination Survey 2001–2006. Sex Transm Dis. 2010;37:399–405.PubMedGoogle Scholar
  23. 23.
    Eddy DM. How to think about screening. In: Eddy DM, editor. Common screening tests. Philadelphia: American College of Physicians; 1991.Google Scholar
  24. 24.
    Rooney JF, Felser JM, Ostrove JM, Straus SE. Acquisition of genital herpes from an asymptomatic sexual partner. N Engl J Med. 1986;314:1561–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116:197–202.PubMedGoogle Scholar
  26. 26.
    Herpes Resource Center. 2011. (Accessed 2011, at
  27. 27.
    Fife KH, Van Der Pol B, Roth AM, et al. Implementation of routine access to herpes simplex virus type 2 antibody testing in a public health sexually transmitted disease clinic. Sex Transm Dis. 2009;36:724–8.PubMedCrossRefGoogle Scholar
  28. 28.
    • Warren T, Gilbert L, Mark H. Availability of serologic and virologic testing for herpes simplex virus in the largest sexually transmitted disease clinics in the United States. Sex Transm Dis. 2011;38:267–9. This articles suggests that although GH testing is recommended as discussed in this review, the majority of clinics screening clients of STI’s do not have access to virologic or serologic screening tests.PubMedGoogle Scholar
  29. 29.
    Corey L, Wald A, et al. Genital Herpes. In: Holmes KK, Sparling PF, Mardh P, editors. Sexually transmitted diseases. New York: McGraw-Hill; 2008.Google Scholar
  30. 30.
    Leone P. Genital Herpes. In: JD Klausner and EW Hook, editors. Current Diagnosis and Treatment: Sexually Transmitted Diseases. McGraw-Hill Co. Inc; 2007.Google Scholar
  31. 31.
    Roizman B, Knipe KD, Whitley RJ. The replication of Herpes Simplex viruses. In: Knipe DM, Howley P, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, editors. Fields’ virology. 5th ed. New York: Lippincott Williams and Wilkins; 2007.Google Scholar
  32. 32.
    Bradshaw CS, Tabrizi SN, Read TR, et al. Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. J Infect Dis. 2006;193:336–45.PubMedCrossRefGoogle Scholar
  33. 33.
    Lautenschlager S, Eichmann A. The heterogeneous clinical spectrum of genital herpes. Dermatology. 2001;202:211–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Fleming DT, Leone P, Esposito D, et al. Herpes virus type 2 infection and genital symptoms in primary care patients. Sex Transm Dis. 2006;33:416–21.PubMedCrossRefGoogle Scholar
  35. 35.
    Mosunjac M, Park J, Wang W, et al. Genital and perianal herpes simplex simulating neoplasia in patients with AIDS. AIDS Patient Care STDS. 2009;23:153–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55:1–94.PubMedGoogle Scholar
  37. 37.
    Strick LB, Wald A. Diagnostics for herpes simplex virus: is PCR the new gold standard? Mol Diagn Ther. 2006;10:17–28.PubMedGoogle Scholar
  38. 38.
    Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. 1983;98:958–72.PubMedGoogle Scholar
  39. 39.
    Wald A, Huang ML, Carrell D, Selke S, Corey L. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003;188:1345–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Turchek BM, Huang YT. Evaluation of ELVIS HSV ID/Typing System for the detection and typing of herpes simplex virus from clinical specimens. J Clin Virol. 1999;12:65–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Ratnam S, Severini A, Zahariadis G, Petric M, Romanowski B. The diagnosis of genital herpes - beyond culture: an evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology. Can J Infect Dis Med Microbiol. 2007;18:233–40.PubMedGoogle Scholar
  42. 42.
    Cone RW, Hobson AC, Palmer J, Remington M, Corey L. Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. J Infect Dis. 1991;164:757–60.PubMedCrossRefGoogle Scholar
  43. 43.
    Coyle PV, O’Neill HJ, McCaughey C, Wyatt DE, McBride MO. Clinical utility of a nested nucleic acid amplification format in comparison to viral culture for the diagnosis of mucosal herpes simplex infection in a genitourinary medicine setting. BMC Infect Dis. 2001;1:11.PubMedCrossRefGoogle Scholar
  44. 44.
    Jerome KR, Huang ML, Wald A, Selke S, Corey L. Quantitative stability of DNA after extended storage of clinical specimens as determined by real-time PCR. J Clin Microbiol. 2002;40:2609–11.PubMedCrossRefGoogle Scholar
  45. 45.
    FDA approved nucleic acid amplification techniques. (Accessed 2011, at
  46. 46.
    Scott LJ, Gunson RN, Carman WF, Winter AJ. A new multiplex real-time PCR test for HSV1/2 and syphilis: an evaluation of its impact in the laboratory and clinical setting. Sex Transm Infect. 2010;86:537–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Suntoke TR, Hardick A, Tobian AA, et al. Evaluation of multiplex real-time PCR for detection of Haemophilus ducreyi, Treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the Rakai District, Uganda. Sex Transm Infect. 2009;85:97–101.PubMedCrossRefGoogle Scholar
  48. 48.
    Strick L, Wald A. Type-specific testing for herpes simplex virus. Expert Rev Mol Diagn. 2004;4:443–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Ashley RaC L. Herpes simplex viruses and B virus. 6th ed. Wahsington D.C: American Public Health Association; 1989.Google Scholar
  50. 50.
    Ashley RL, Militoni J, Lee F, Nahmias A, Corey L. Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera. J Clin Microbiol. 1988;26:662–7.PubMedGoogle Scholar
  51. 51.
    Groen J, Van Dijk G, Niesters HG, Van Der Meijden WI, Osterhaus AD. Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum. J Clin Microbiol. 1998;36:845–7.PubMedGoogle Scholar
  52. 52.
    Turner KR, Wong EH, Kent CK, Klausner JD. Serologic herpes testing in the real world: validation of new type-specific serologic herpes simplex virus tests in a public health laboratory. Sex Transm Dis. 2002;29:422–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35:S173–82.PubMedCrossRefGoogle Scholar
  54. 54.
    • Biraro S, Mayaud P, Morrow RA, Grosskurth H, Weiss HA. Performance of commercial herpes simplex virus type-2 antibody tests using serum samples from sub-Saharan Africa: A systematic review and meta-analysis. Sex Transm Dis 2010. This meta-analysis provides an excellent discussion of the performance of serologic tests in Sub-Saharan Africa. It compares HereSelect and the Kalon assays to western blot. If provides a discussion of how the use of different ELISA index values as the cutoff for a positive test affect test performance. Google Scholar
  55. 55.
    Morrow RA, Brown ZA. Common use of inaccurate antibody assays to identify infection status with herpes simplex virus type 2. Am J Obstet Gynecol. 2005;193:361–2.PubMedCrossRefGoogle Scholar
  56. 56.
    Prince HE, Ernst CE, Hogrefe WR. Evaluation of an enzyme immunoassay system for measuring herpes simplex virus (HSV) type 1-specific and HSV type 2-specific IgG antibodies. J Clin Lab Anal. 2000;14:13–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Morrow RA, Friedrich D, Krantz E. Performance of the focus and Kalon enzyme-linked immunosorbent assays for antibodies to herpes simplex virus type 2 glycoprotein G in culture-documented cases of genital herpes. J Clin Microbiol. 2003;41:5212–4.PubMedCrossRefGoogle Scholar
  58. 58.
    Ashley RL, Wu L, Pickering JW, Tu MC, Schnorenberg L. Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies. J Clin Microbiol. 1998;36:294–5.PubMedGoogle Scholar
  59. 59.
    Eis-Hubinger AM, Daumer M, Matz B, Schneweis KE. Evaluation of three glycoprotein G2-based enzyme immunoassays for detection of antibodies to herpes simplex virus type 2 in human sera. J Clin Microbiol. 1999;37:1242–6.PubMedGoogle Scholar
  60. 60.
    Golden MR, Ashley-Morrow R, Swenson P, Hogrefe WR, Handsfield HH, Wald A. Herpes simplex virus type 2 (HSV-2) Western blot confirmatory testing among men testing positive for HSV-2 using the focus enzyme-linked immunosorbent assay in a sexually transmitted disease clinic. Sex Transm Dis. 2005;32:771–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Mark HD, Nanda JP, Roberts J, Rompalo A, Melendez JH, Zenilman J. Performance of focus ELISA tests for HSV-1 and HSV-2 antibodies among university students with no history of genital herpes. Sex Transm Dis. 2007;34:681–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Summerton J, Riedesel M, Laeyendecker O, et al. Effect of sexually transmitted disease (STD) coinfections on performance of three commercially available immunosorbent assays used for detection of herpes simplex virus type 2-specific antibody in men attending Baltimore, Maryland, STD clinics. Clin Vaccine Immunol. 2007;14:1545–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Ashley-Morrow R, Nollkamper J, Robinson NJ, Bishop N, Smith J. Performance of focus ELISA tests for herpes simplex virus type 1 (HSV-1) and HSV-2 antibodies among women in ten diverse geographical locations. Clin Microbiol Infect. 2004;10:530–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Hogrefe W, Su X, Song J, Ashley R, Kong L. Detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in African sera by using recombinant gG2, Western blotting, and gG2 inhibition. J Clin Microbiol. 2002;40:3635–40.PubMedCrossRefGoogle Scholar
  65. 65.
    HerpeSeect 2 ELISA IgG package insert (Accessed 2011, at
  66. 66.
    Greer L, Wendel Jr GD. Rapid diagnostic methods in sexually transmitted infections. Infect Dis Clin North Am. 2008;22:601–17.PubMedCrossRefGoogle Scholar
  67. 67.
    Ashley RL, Eagleton M, Pfeiffer N. Ability of a rapid serology test to detect seroconversion to herpes simplex virus type 2 glycoprotein G soon after infection. J Clin Microbiol. 1999;37:1632–3.PubMedGoogle Scholar
  68. 68.
    Morrow RA, Friedrich D, Meier A, Corey L. Use of “biokit HSV-2 Rapid Assay” to improve the positive predictive value of Focus HerpeSelect HSV-2 ELISA. BMC Infect Dis. 2005;5:84.PubMedCrossRefGoogle Scholar
  69. 69.
    Douglas Jr JM, Berman SM. Screening for HSV-2 infection in STD clinics and beyond: a few answers but more questions. Sex Transm Dis. 2009;36:729–31.PubMedCrossRefGoogle Scholar
  70. 70.
    Hook EW, Leone P. Time to translate new knowledge into practice: a call for a national genital herpes control program. J Infect Dis. 2006;194:6–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Van de Perre P, Segondy M, Foulongne V, et al. Herpes simplex virus and HIV-1: deciphering viral synergy. Lancet Infect Dis. 2008;8:490–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Modjarrad K, Vermund SH. Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis. 2010;10:455–63.PubMedCrossRefGoogle Scholar
  73. 73.
    Glynn JR, Biraro S, Weiss HA. Herpes simplex virus type 2: a key role in HIV incidence. AIDS. 2009;23:1595–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Mark KE, Wald A, Magaret AS, et al. Rapidly cleared episodes of oral and anogenital herpes simplex virus shedding in HIV-infected adults. J Acquir Immune Defic Syndr. 2010;54:482–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Schacker T, Zeh J, Hu HL, Hill E, Corey L. Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men. J Infect Dis. 1998;178:1616–22.PubMedCrossRefGoogle Scholar
  76. 76.
    Bollen LJ, Whitehead SJ, Mock PA, et al. Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: possibility to further decrease transmission? AIDS. 2008;22:1169–76.PubMedCrossRefGoogle Scholar
  77. 77.
    Nagot N, Ouedraogo A, Foulongne V, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007;356:790–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Whitley RJ. Neonatal herpes simplex virus infections. J Med Virol 1993;Suppl 1:13–21.Google Scholar
  79. 79.
    Riley LE. Herpes simplex virus. Semin Perinatol. 1998;22:284–92.PubMedCrossRefGoogle Scholar
  80. 80.
    Whitley RJ, Corey L, Arvin A, et al. Changing presentation of herpes simplex virus infection in neonates. J Infect Dis. 1988;158:109–16.PubMedCrossRefGoogle Scholar
  81. 81.
    Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997;337:509–15.PubMedCrossRefGoogle Scholar
  82. 82.
    Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. 2003;289:203–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Prober CG, Sullender WM, Yasukawa LL, Au DS, Yeager AS, Arvin AM. Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes simplex virus infections. N Engl J Med. 1987;316:240–4.PubMedCrossRefGoogle Scholar
  84. 84.
    Wald A, Krantz E, Selke S, Lairson E, Morrow RA, Zeh J. Knowledge of partners’ genital herpes protects against herpes simplex virus type 2 acquisition. J Infect Dis. 2006;194:42–52.PubMedCrossRefGoogle Scholar
  85. 85.
    Celum C, Wald A, Hughes J, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:2109–19.PubMedCrossRefGoogle Scholar
  86. 86.
    Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med. 2010;362:427–39.PubMedCrossRefGoogle Scholar
  87. 87.
    Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008;358:1560–71.PubMedCrossRefGoogle Scholar
  88. 88.
    • Barnabas RV, Wasserheit JN, Huang Y, et al. Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic Syndr. 2011;57:238–44. The study provides evidence that HSV-2 infection increases risk of HIV acquisition. However, coinfection with HIV and HSV-2 does not lead to more rapid HIV progressions as determined by time to ART initiation.PubMedCrossRefGoogle Scholar
  89. 89.
    Ioannidis JP, Collier AC, Cooper DA, et al. Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis. 1998;178:349–59.PubMedGoogle Scholar
  90. 90.
    • Lingappa JR, Baeten JM, Wald A, et al. Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet. 2010;375:824–33. This RCT demonstrated a modest reduction in HIV progression as determined by a falling CD4 count in HIV and HSV-2 infected persons taking high dose acyclovir. PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA

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