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High seroprevalence of antibodies against Kaposi’s sarcoma-associated herpesvirus (KSHV) among HIV-1-infected children and adolescents in a non-endemic population

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Abstract

Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi’s sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Currently, only limited prevalence data for HHV-8 infection in HIV-infected children living in non-endemic areas are available. This multicenter cross-sectional study was conducted in four university hospitals in Germany specializing in pediatric HIV care. Stored serum specimens obtained from 207 vertically HIV-1-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Logistic regression was used to assess independent risk factors associated with HHV-8 seropositivity. The overall HHV-8 seroprevalence was 24.6 % (n = 51/207) without significant differences related to sex, age, or ethnicity. In univariate analysis, HHV-8 seropositivity was significantly associated with a child having being born outside Germany, maternal origin from sub-Saharan Africa, a history of breastfeeding, CDC immunologic category 3, and deferred initiation of antiretroviral therapy (>24 months of age). In multivariate analysis, a child’s birth outside Germany was the only significant risk factor for HHV-8 seropositivity (odds ratio 3.98; 95 % confidence interval 1.27–12.42). HHV-8-associated malignancies were uncommon; only one patient had a history of KS. Serum specimen of vertically HIV-infected children and adolescents living in Germany showed a high HHV-8 seroprevalence. These findings suggest that primary HHV-8 infection—a risk factor for KS and other HHV-8-associated malignancies—occurs early in life. Thus, management of perinatally HIV-infected children should include testing for HHV-8 coinfection and should consider future risks of HHV-8-associated malignancies.

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References

  1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266(5192):1865–1869

    Article  CAS  PubMed  Google Scholar 

  2. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332(18):1186–1191

    Article  CAS  PubMed  Google Scholar 

  3. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, d’Agay MF, Clauvel JP, Raphael M, Degos L et al (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86(4):1276–1280

    CAS  PubMed  Google Scholar 

  4. Antman K, Chang Y (2000) Kaposi’s sarcoma. N Engl J Med 342(14):1027–1038

    Article  CAS  PubMed  Google Scholar 

  5. Dow DE, Cunningham CK, Buchanan AM (2014) A review of human herpesvirus 8, the Kaposi’s sarcoma-associated herpesvirus, in the pediatric population. J Pediatric Infect Dis Soc 3(1):66–76

    Article  PubMed  Google Scholar 

  6. Labo N, Miley W, Benson CA, Campbell TB, Whitby D (2015) Epidemiology of Kaposi’s sarcoma-associated herpesvirus in HIV-1-infected US persons in the era of combination antiretroviral therapy. AIDS 29(10):1217–1225

    Article  CAS  PubMed  Google Scholar 

  7. Mani D, Neil N, Israel R, Aboulafia DM (2009) A retrospective analysis of AIDS-associated Kaposi’s sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells/mm(3). J Int Assoc Physicians AIDS Care (Chic) 8(5):279–285

    Article  Google Scholar 

  8. Guadalupe M, Pollock BH, Westbrook S, Redding S, Bullock D, Anstead G, Agan BK, Marconi VC, Barbieri S, Sankar V, Rebeles J, Flahive Y, Schoolfield J, Wang L, Lei X, Dow D, Yeh CK, Dang H, Infante AJ, Gao SJ (2011) Risk factors influencing antibody responses to Kaposi’s sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy. J Acquir Immune Defic Syndr 56(1):83–90

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dedicoat M, Newton R (2003) Review of the distribution of Kaposi’s sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi’s sarcoma. Br J Cancer 88(1):1–3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mayama S, Cuevas LE, Sheldon J, Omar OH, Smith DH, Okong P, Silvel B, Hart CA, Schulz TF (1998) Prevalence and transmission of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents. Int J Cancer 77(6):817–820

    Article  CAS  PubMed  Google Scholar 

  11. Butler LM, Were WA, Balinandi S, Downing R, Dollard S, Neilands TB, Gupta S, Rutherford GW, Mermin J (2011) Human herpesvirus 8 infection in children and adults in a population-based study in rural Uganda. J Infect Dis 203(5):625–634

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sarmati L (2004) HHV-8 infection in African children. Herpes 11(2):50–53

    PubMed  Google Scholar 

  13. Plancoulaine S, Abel L, van Beveren M, Tregouet DA, Joubert M, Tortevoye P, de The G, Gessain A (2000) Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population. Lancet 356(9235):1062–1065

    Article  CAS  PubMed  Google Scholar 

  14. Mbulaiteye SM, Pfeiffer RM, Whitby D, Brubaker GR, Shao J, Biggar RJ (2003) Human herpesvirus 8 infection within families in rural Tanzania. J Infect Dis 187(11):1780–1785

    Article  PubMed  Google Scholar 

  15. Lyall EG, Patton GS, Sheldon J, Stainsby C, Mullen J, O’Shea S, Smith NA, De Ruiter A, McClure MO, Schulz TF (1999) Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers. Pediatr Infect Dis J 18(9):795–799

    Article  CAS  PubMed  Google Scholar 

  16. Sarmati L, Carlo T, Rossella S, Montano M, Adalgisa P, Rezza G, Andreoni M (2004) Human herpesvirus-8 infection in pregnancy and labor: lack of evidence of vertical transmission. J Med Virol 72(3):462–466

    Article  PubMed  Google Scholar 

  17. Dukers NH, Rezza G (2003) Human herpesvirus 8 epidemiology: what we do and do not know. AIDS 17(12):1717–1730

    Article  PubMed  Google Scholar 

  18. Preiser W, Szep NI, Lang D, Doerr HW, Rabenau HF (2001) Kaposi’s sarcoma-associated herpesvirus seroprevalence in selected german patients: evaluation by different test systems. Med Microbiol Immunol 190(3):121–127

    CAS  PubMed  Google Scholar 

  19. Martro E, Bulterys M, Stewart JA, Spira TJ, Cannon MJ, Thacher TD, Bruns R, Pellett PE, Dollard SC (2004) Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi’s sarcoma. J Med Virol 72(1):126–131

    Article  CAS  PubMed  Google Scholar 

  20. Renne R, Zhong W, Herndier B, McGrath M, Abbey N, Kedes D, Ganem D (1996) Lytic growth of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2(3):342–346

    Article  CAS  PubMed  Google Scholar 

  21. Gärtner BC, Kloss A, Kaul H, Sester U, Roemer K, Pees H, Köhler H, Mueller-Lantzsch N (2003) Risk of occupational human herpesvirus 8 infection for health care workers. J Clin Microbiol 41(5):2156–2157

    Article  PubMed  PubMed Central  Google Scholar 

  22. Center of Disease Control and Prevention (1994) 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Center of Disease Control and Prevention. Accessed 22 May 2015

  23. Deutsche AIDS-Gesellschaft e.V. (DAIG) [German AIDS Society] (2011) Deutsch-Österreichische Leitlinien zur HIV-Therapie in der Schwangerschaft und bei HIV-exponierten Neugeborenen (Stand September 2011). Available at: http://www.rki.de/DE/Content/InfAZ/HIVAIDS/Therapie/Leitlinien/PDF_D_A_schwanger.pdf. Accessed 20 June 2015

  24. Anderson LA, Li Y, Graubard BI, Whitby D, Mbisa G, Tan S, Goedert JJ, Engels EA (2008) Human herpesvirus 8 seroprevalence among children and adolescents in the United States. Pediatr Infect Dis J 27(7):661–664

    Article  PubMed  Google Scholar 

  25. Blauvelt A, Sei S, Cook PM, Schulz TF, Jeang KT (1997) Human herpesvirus 8 infection occurs following adolescence in the United States. J Infect Dis 176(3):771–774

    Article  CAS  PubMed  Google Scholar 

  26. Ilboudo D, Simpore J, Sanou DS, Karou D, Sia DJ, Ouermi D, Bisseye C, Sagna T, Odolini S, Buelli F, Pietra V, Pignatelli S, Gnoula C, Nikiema JB, Castelli F (2009) Mother-to-child HIV and HHV-8 transmission in neonates at Saint Camille medical centre in Burkina Faso. Pak J Biol Sci 12(12):908–913

    Article  CAS  PubMed  Google Scholar 

  27. Brayfield BP, Kankasa C, West JT, Muyanga J, Bhat G, Klaskala W, Mitchell CD, Wood C (2004) Distribution of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 in maternal saliva and breast milk in Zambia: implications for transmission. J Infect Dis 189(12):2260–2270

    Article  PubMed  Google Scholar 

  28. Crabtree KL, Wojcicki JM, Minhas V, Smith DR, Kankasa C, Mitchell CD, Wood C (2014) Risk factors for early childhood infection of human herpesvirus-8 in Zambian children: the role of early childhood feeding practices. Cancer Epidemiol Biomark Prev 23(2):300–308

    Article  Google Scholar 

  29. Phipps W, Saracino M, Selke S, Huang ML, Jaoko W, Mandaliya K, Wald A, Casper C, McClelland RS (2014) Oral HHV-8 replication among women in Mombasa, Kenya. J Med Virol 86(10):1759–1765

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen N, Nelson KE, Jenkins FJ, Suriyanon V, Duerr A, Costello C, Robison V, Jacobson LP (2004) Seroprevalence of human herpesvirus 8 infection in Northern Thailand. Clin Infect Dis 39(7):1052–1058

    Article  PubMed  Google Scholar 

  31. Malope BI, Pfeiffer RM, Mbisa G, Stein L, Ratshikhopha EM, O’Connell DL, Sitas F, MacPhail P, Whitby D (2007) Transmission of Kaposi sarcoma-associated herpesvirus between mothers and children in a South African population. J Acquir Immune Defic Syndr 44(3):351–355

    Article  PubMed  Google Scholar 

  32. Minhas V, Crabtree KL, Chao A, M’Soka TJ, Kankasa C, Bulterys M, Mitchell CD, Wood C (2008) Early childhood infection by human herpesvirus 8 in Zambia and the role of human immunodeficiency virus type 1 coinfection in a highly endemic area. Am J Epidemiol 168(3):311–320

    Article  PubMed Central  Google Scholar 

  33. Wakeham K, Webb EL, Sebina I, Nalwoga A, Muhangi L, Miley W, Johnston WT, Ndibazza J, Whitby D, Newton R, Elliott AM (2013) Risk factors for seropositivity to Kaposi sarcoma-associated herpesvirus among children in Uganda. J Acquir Immune Defic Syndr 63(2):228–233

    Article  PubMed  PubMed Central  Google Scholar 

  34. Uldrick TS, Whitby D (2011) Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett 305(2):150–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Arkin LM, Cox CM, Kovarik CL (2009) Kaposi’s sarcoma in the pediatric population: the critical need for a tissue diagnosis. Pediatr Infect Dis J 28(5):426–428

    Article  PubMed  Google Scholar 

  36. Gantt S, Kakuru A, Wald A, Walusansa V, Corey L, Casper C, Orem J (2010) Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children. Pediatr Blood Cancer 54(5):670–674

    Article  PubMed  PubMed Central  Google Scholar 

  37. Cattelan AM, Calabro ML, Gasperini P, Aversa SM, Zanchetta M, Meneghetti F, De Rossi A, Chieco-Bianchi L (2001) Acquired immunodeficiency syndrome-related Kaposi’s sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome. J Natl Cancer Inst Monogr 28:44–49

    PubMed  Google Scholar 

  38. Paparizos VA, Kyriakis KP, Papastamopoulos V, Hadjivassiliou M, Stavrianeas NG (2002) Response of AIDS-associated Kaposi sarcoma to highly active antiretroviral therapy alone. J Acquir Immune Defic Syndr 30(2):257–258

    Article  PubMed  Google Scholar 

  39. Twichell S, Loechelt B, Rana S, Rakusan T, Wheeling J, Bohannon B, Patel P, Dominguez K, Consortiums at PaL (2010) Trends in incidence of AIDS-defining and non-AIDS-defining cancer among HIV-infected children in the US, 1984 to 2006. Paper presented at the 17th conference on retroviruses and opportunistic infections, San Francisco

  40. Helleberg M, Gerstoft J, Afzal S, Kronborg G, Larsen CS, Pedersen C, Bojesen SE, Nordestgaard BG, Obel N (2014) Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV. AIDS 28(10):1499–1508

    Article  PubMed  Google Scholar 

  41. Siberry GK, Abzug MJ, Nachman S, Brady MT, Dominguez KL, Handelsman E, Mofenson LM, Nesheim S, Panel on Opportunistic Infections in HIVE, Children HI-I (2013) Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. Pediatr Infect Dis J 32(Suppl 2):i-KK4

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Acknowledgments

We thank Martin J. Raftery, MD, Charité University Medicine Berlin, Germany, for a critical review of the manuscript. We also thank all patients and their families who participated in the study.

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Authors and Affiliations

  1. Department of Pediatric Pneumology and Immunology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Cornelia Feiterna-Sperling & Renate Krüger

  2. Department of Pediatrics, University Hospital Frankfurt, Goethe University, Frankfurt, Germany

    Christoph Königs

  3. Ludwig-Maximilians-University of Munich, Dr. von Haunersches Kinderspital, Munich, Germany

    Gundula Notheis

  4. Medical Faculty Mannheim, University Children’s Hospital, Heidelberg University, Heidelberg, Germany

    Bernd Buchholz

  5. Department of Obstetrics, Charité University Medicine Berlin, Berlin, Germany

    Katharina Weizsäcker

  6. Max von Pettenkofer-Institut, Ludwig-Maximilians-University of Munich, Munich, Germany

    Josef Eberle

  7. German Association of Physicians in HIV Care, Berlin, Germany

    Nikola Hanhoff

  8. Institute of Microbiology and Hygiene, University of Saarland Medical School, Homburg/Saar, Germany

    Barbara Gärtner

  9. Institute of Medical Virology, Helmut-Ruska-Haus, Charité University Medicine Berlin, Berlin, Germany

    Harald Heider, Detlev H. Krüger & Jörg Hofmann

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  1. Cornelia Feiterna-Sperling
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Correspondence to Cornelia Feiterna-Sperling.

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Feiterna-Sperling, C., Königs, C., Notheis, G. et al. High seroprevalence of antibodies against Kaposi’s sarcoma-associated herpesvirus (KSHV) among HIV-1-infected children and adolescents in a non-endemic population. Med Microbiol Immunol 205, 425–434 (2016). https://doi.org/10.1007/s00430-016-0458-x

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