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Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study

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Abstract

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

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References

  1. Guibert G, Warszawski J, Le Chenadec J, Blanche S, Benmebarek Y, Mandelbrot L et al (2009) Decreased risk of congenital cytomegalovirus infection in children born to HIV-1-infected mothers in the era of highly active antiretroviral therapy. Clin Infect Dis 48(11):1516–1525

    Article  PubMed  Google Scholar 

  2. Revello MG, Gerna G (2002) Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev 15(4):680–715

    Article  PubMed Central  PubMed  Google Scholar 

  3. Benoist G, Leruez-Ville M, Magny JF, Jacquemard F, Salomon LJ, Ville Y (2013) Management of pregnancies with confirmed cytomegalovirus fetal infection. Fetal Diagn Ther 33(4):203–214

    Article  PubMed  Google Scholar 

  4. Kenneson A, Cannon MJ (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 4:253–276

    Article  Google Scholar 

  5. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK (2013) The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 26(1):86–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Leruez-Ville M, Vauloup-Fellous C, Couderc S, Parat S, Castel C, Avettand-Fenoel V et al (2011) Prospective identification of congenital cytomegalovirus infection in newborns using real-time polymerase chain reaction assays in dried blood spots. Clin Infect Dis 52(5):575–581

    Article  CAS  PubMed  Google Scholar 

  7. Wang CJZX, Bialek S, Cannon MJ (2011) Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection. Clin Infect Dis 52:11–13

    Article  Google Scholar 

  8. Yamamoto AY, Mussi-Pinhata MM, Boppana SB, Novak Z, Wagatsuma VM, Oliveira Pde F et al (2010) Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population. Am J Obstet Gynecol 202(3):297 e1–8

  9. Stagno S, Dworsky ME, Torres J, Mesa T, Hirsh T (1982) Prevalence and importance of congenital cytomegalovirus infection in three different populations. J Pediatr 101(6):897–900

    Article  CAS  PubMed  Google Scholar 

  10. Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF (1999) Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics 104(1 Pt 1):55–60

    Article  CAS  PubMed  Google Scholar 

  11. Yow MD, Williamson DW, Leeds LJ, Thompson P, Woodward RM, Walmus BF et al (1988) Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants. Am J Obstet Gynecol 158(5):1189–1195

    Article  CAS  PubMed  Google Scholar 

  12. Lubeck PR, Doerr HW, Rabenau HF (2010) Epidemiology of human cytomegalovirus (HCMV) in an urban region of Germany: what has changed? Med Microbiol Immunol 199(1):53–60

    Article  PubMed  Google Scholar 

  13. Enders G, Daiminger A, Lindemann L, Knotek F, Bader U, Exler S et al (2012) Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996–2010. Med Microbiol Immunol 201(3):303–309

    Article  PubMed  Google Scholar 

  14. Walker SP, Palma-Dias R, Wood EM, Shekleton P, Giles ML (2013) Cytomegalovirus in pregnancy: to screen or not to screen. BMC Pregnancy Childbirth 13:96

    Article  PubMed Central  PubMed  Google Scholar 

  15. Schlesinger Y, Halle D, Eidelman AI, Reich D, Dayan D, Rudensky B et al (2003) Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection. Arch Dis Child Fetal Neonatal Ed 88(5):F371–F374

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Fowler KB, Stagno S, Pass RF (2003) Maternal immunity and prevention of congenital cytomegalovirus infection. J Am Med Assoc 289(8):1008–1011

    Article  Google Scholar 

  17. Berger A, Reitter A, Harter PN, Buxmann H, Allwinn R, Louwen F et al (2011) Problems and challenges in the diagnosis of vertical infection with human cytomegalovirus (CMV): lessons from two accidental cases. J Clin Virol 51(4):285–288

    Article  PubMed  Google Scholar 

  18. Mussi-Pinhata MM, Yamamoto AY, Figueiredo LTM, Cervi MC, Duarte G (1998) Congenital and perinatal cytomegalovirus infection in infants born to mothers infected with human immunodeficiency virus. J Pediatr 132(2):285–290

    Article  CAS  PubMed  Google Scholar 

  19. Doyle M, Atkins JT, Rivera-Matos IR (1996) Congenital cytomegalovirus infection in infants infected with human immunodeficiency virus type 1. Pediatr Infect Dis J 15(12):1102–1106

    Article  CAS  PubMed  Google Scholar 

  20. Duryea EL, Sanchez PJ, Sheffield JS, Jackson GL, Wendel GD, McElwee BS et al (2010) Maternal human immunodeficiency virus infection and congenital transmission of cytomegalovirus. Pediatr Infect Dis J 29(10):915–918

    Article  PubMed  Google Scholar 

  21. Enzensberger R, Braun W, July C, Helm EB, Doerr HW (1991) Prevalence of antibodies to human herpesviruses and hepatitis B virus in patients at different stages of human immunodeficiency virus (HIV) infection. Infection 19(3):140–145

    Article  CAS  PubMed  Google Scholar 

  22. (2009) German–Austrian recommendations for HIV treatment during pregnancy and for newborns exposed to HIV: update 2008. Dtsch Med Wochenschr 134(Suppl 1):S40–S54

  23. Buchholz B, Beichert M, Marcus U, Grubert T, Gingelmaier A, Haberl A et al (2009) German–Austrian recommendations for HIV1-therapy in pregnancy and in HIV1-exposed newborn, update 2008. Eur J Med Res 14(11):461–479

    PubMed Central  PubMed  Google Scholar 

  24. Preiser W, Buxbaum S, Fleckenstein C, Doerr HW (2003) Measurement of CMV DNA levels and CMV-specific CD4-lymphocyte counts in patient specimens: requirements for test quality and practicability in a routine diagnostic service. In: Proesch S, Cinatl J, Scholz M (eds.) New aspects of CMV-related immunopathology, vol 24. Basel, karger, pp 133–148

  25. Buxmann H, Miljak A, Fischer D, Rabenau HF, Doerr HW, Schloesser RL (2009) Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants ≤31 weeks. Acta Paediatr 98(2):270–276

    Article  PubMed  Google Scholar 

  26. Weber B, Hamann A, Ritt B, Rabenau H, Braun W, Doerr HW (1992) Comparison of shell viral culture and serology for the diagnosis of human cytomegalovirus infection in neonates and immunocompromised subjects. Clin Investig 70(6):503–507

    CAS  PubMed  Google Scholar 

  27. Laboratory Diagnostic in viral diseases relevant to pregnancy (2014) AWMF 0093/001

  28. Viljoen J, Tuaillon E, Nagot N, Danaviah S, Peries M, Padayachee P et al (2015) Cytomegalovirus, and possibly Epstein-Barr virus, shedding in breast milk is associated with HIV-1 transmission by breastfeeding. AIDS (London, England) 29(2):145–153

    Article  Google Scholar 

  29. Britt W (2015) Controversies in the natural history of congenital human cytomegalovirus infection: the paradox of infection and disease in offspring of women with immunity prior to pregnancy. Med Microbiol Immunol 204(3):263–271

    Article  CAS  PubMed  Google Scholar 

  30. Doerr HW, Cinatl J (2012) Recent publications in medical microbiology and immunology: a retrospective. Med Microbiol Immunol 201(1):1–5

    Article  CAS  PubMed  Google Scholar 

  31. Lipitz S, Yinon Y, Malinger G, Yagel S, Levit L, Hoffman C et al (2013) Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging. Ultrasound Obstet Gynecol 41(5):508–514

    Article  CAS  PubMed  Google Scholar 

  32. Ross SBS (2004) Congenital cytomegalovirus infection: outcome and diagnosis. Semin Pediatr Infect Dis 16:44–49

    Article  Google Scholar 

  33. Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M et al (2003) Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 143(1):16–25

    Article  CAS  PubMed  Google Scholar 

  34. Schleiss MR (2008) Congenital cytomegalovirus infection: update on management strategies. Curr Treat Options Neurol 10(3):186–192

    Article  PubMed Central  PubMed  Google Scholar 

  35. Frenzel K, Lehmann J, Kruger DH, Martin-Parras L, Uharek L, Hofmann J (2014) Combination of immunoglobulins and natural killer cells in the context of CMV and EBV infection. Med Microbiol Immunol 203(2):115–123

    Article  CAS  PubMed  Google Scholar 

  36. Buxmann H, Stackelberg OM, Schlosser RL, Enders G, Gonser M, Meyer-Wittkopf M et al (2012) Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med 40(4):439–446

    PubMed  Google Scholar 

  37. Nigro G, Adler SP, La Torre R, Best AM (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353(13):1350–1362

    Article  CAS  PubMed  Google Scholar 

  38. Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A et al (2014) A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 370(14):1316–1326

    Article  CAS  PubMed  Google Scholar 

  39. Nigro G, Capretti I, Manganello AM, Best AM, Adler SP (2015) Primary maternal cytomegalovirus infections during pregnancy: association of CMV hyperimmune globulin with gestational age at birth and birth weight. J Matern Fetal Neonatal Med 28(2):168–171

    Article  CAS  PubMed  Google Scholar 

  40. Plotkin S (2015) The history of vaccination against cytomegalovirus. Med Microbiol Immunol 204(3):247–254

    Article  CAS  PubMed  Google Scholar 

  41. Boppana SB, Ross SA, Novak Z, Shimamura M, Tolan RW Jr, Palmer AL et al (2010) Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. J Am Med Assoc 303(14):1375–1382

    Article  CAS  Google Scholar 

  42. Vauloup-Fellous C, Ducroux A, Couloigner V, Marlin S, Picone O, Galimand J et al (2007) Evaluation of cytomegalovirus (CMV) DNA quantification in dried blood spots: retrospective study of CMV congenital infection. J Clin Microbiol 45(11):3804–3806

    Article  PubMed Central  PubMed  Google Scholar 

  43. Bhattarakosol PKE, Praisuwanna P (2011) HIV infection might not increase the intrauterine transmission rate of CMV and HSV in patients with co-infection. J Pediatr Infect Dis 6:103–110

    Google Scholar 

  44. Frederick T, Homans J, Spencer L, Kramer F, Stek A, Operskalski E et al (2012) The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants. Clinical Infect Dis 55(6):877–884

    Article  CAS  Google Scholar 

  45. Gratacap-Cavallier B, Morand P, Dutertre N, Bosson JL, Baccard-Longere M, Jouk PS et al (1998) Cytomegalovirus infection in pregnant women: seroepidemiological prospective study in 1018 women in Isere. J Gynecol Obstet Biol Reprod 27(2):161–166

    CAS  Google Scholar 

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Acknowledgments

The authors would like to acknowledge Dr. Andrew Bisits, MD, FRANZCOG, Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia, for statistical and writing assistance during the development of this article.

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Correspondence to A. Reitter.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethics approval was obtained from the Ethics Committee at the JW-Goethe University Frankfurt (Number30/13).

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Reitter, A., Buxmann, H., Haberl, A.E. et al. Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study. Med Microbiol Immunol 205, 63–71 (2016). https://doi.org/10.1007/s00430-015-0427-9

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  • DOI: https://doi.org/10.1007/s00430-015-0427-9

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