Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children

BMC Infectious Diseases

Sheila C Dollard²  D Scott Schmid²  Jing Guo³  Will Hendley²  Minal Amin²  Karen Wu³  Cynthia Stover³  Karen Mask¹  Delaney Johnson¹  Philip R Dollard¹  Rebekah Clark¹  Jennifer D Stowell³  Michael J Cannon³ 

[1] Emory University, Atlanta, GA, USA;National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA;National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop E-86, Atlanta 30333, GA, USA

关键词: Pregnancy;    Behavior;    Awareness;    Congenital;    Cytomegalovirus;   

Others  :  1122075
DOI  :  10.1186/s12879-014-0569-1

 received in 2014-05-12, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

Background

To better understand potential transmission risks from contact with the body fluids of children, we monitored the presence and amount of CMV shedding over time in healthy CMV-seropositive children.

Methods

Through screening we identified 36 children from the Atlanta, Georgia area who were CMV-seropositive, including 23 who were shedding CMV at the time of screening. Each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine daily.

Results

Prevalence of shedding was highly correlated with initial shedding status: children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those not shedding at the screening visit had CMV DNA in 16% of follow-up saliva specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730 copies/mL in urine (P = 0.01), while the viral load for the 75th percentile was nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine. Younger age was significantly associated with higher viral loads, especially for saliva (P < 0.001). Shedding prevalence and viral loads were relatively stable over time. All children who were shedding at the screening visit were still shedding at least some days during weeks 11 and 12, and median and mean viral loads did not change substantially over time.

Conclusions

Healthy CMV-seropositive children can shed CMV for months at high, relatively stable levels. These data suggest that behavioral prevention messages need to address transmission via both saliva and urine, but also need to be informed by the potentially higher risks posed by saliva and by exposures to younger children.

【 授权许可】

   
2014 Cannon et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Cannon MJ: Congenital cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol 2009, 46S:S6-S10.
• [2]Dollard SC, Grosse SD, Ross DS: New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 2007, 17(5):355-363.
• [3]Mocarski ES Jr, Shenk T, Pass RF: Cytomegaloviruses. In Fields’ Virology. 5th edition. Edited by Knipe DM, Howley PM. Lippincott Williams & Wilkins, Philadelphia; 2007:2702-2772.
• [4]Adler SP, Finney JW, Manganello AM, Best AM: Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: a randomized controlled trial. Pediatr Infect Dis J 1996, 15(3):240-246.
• [5]Cannon MJ, Davis KF: Washing our hands of the congenital cytomegalovirus disease epidemic.BMC Public Health 2005, 5(1):70.
• [6]Vauloup-Fellous C, Picone O, Cordier A-G, Parent-du-Chatelet I, Senat M-V, Frydman R, Grangeot-Keros L: Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital. J Clin Virol 2009, 46S:S49-S53.
• [7]Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, Corey L, Hill J, Davis E, Flanigan C, Cloud G: Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 2009, 360(12):1191-1199.
• [8]Sung H, Schleiss MR: Update on the current status of cytomegalovirus vaccines. Expert Rev Vaccines 2010, 9(11):1303-1314.
• [9]Nigro G, Adler SP, La Torre R, Best AM: Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005, 353(13):1350-1362.
• [10]Johnson J, Anderson B, Pass RF: Prevention of maternal and congenital cytomegalovirus infection. Clin Obstet Gynecol 2012, 55(2):521-530.
• [11]Griffiths PD: Progress towards interrupting intrauterine transmission of cytomegalovirus? Rev Med Virol 2006, 16(1):1-4.
• [12]Staras SA, Flanders WD, Dollard SC, Pass RF, McGowan JE Jr, Cannon MJ: Influence of sexual activity on cytomegalovirus seroprevalence in the United States, 1988–1994. Sex Transm Dis 2008, 35(5):472-479.
• [13]Fowler KB, Pass RF: Risk factors for congenital cytomegalovirus infection in the offspring of young women: exposure to young children and recent onset of sexual activity. Pediatrics 2006, 118(2):e286-e292.
• [14]Hyde TB, Schmid DS, Cannon MJ: Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 2010, 20(5):311-326.
• [15]Barbi M, Binda S, Primache V, Caroppo S, Dido P, Guidotti P, Corbetta C, Melotti D: Cytomegalovirus DNA detection in Guthrie cards: a powerful tool for diagnosing congenital infection. J Clin Virol 2000, 17(3):159-165.
• [16]Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, Britt WJ: Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 2005, 146(6):817-823.
• [17]Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ, Dollard SC: Use of screening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection. J Pediatr 2010, 157(2):191-197.
• [18]Cannon MJ, Hyde TB, Schmid DS: Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol 2011, 21(4):240-255.
• [19]Murph JR, Bale JF: The natural history of acquired cytomegalovirus infection among children in group day care. Am J Dis Child 1988, 142:843-846.
• [20]Strom J: A study of infections and illnesses in a day nursery based on inclusion-bearing cells in the urine and infectious agent in feces, urine and nasal secretion. Scand J Infect Dis 1979, 11:265-269.
• [21]Levinsohn EM, Foy HM, Kenny GE, Wentworth BB, Grayston JT: Isolation of cytomegalovirus from a cohort of 100 infants throughout the first year of life. Proc Soc Exp Biol Med 1969, 132(3):957-962.
• [22]Stagno S, Pass RF, Dworsky ME, Alford CA: Congenital and perinatal cytomegalovirus infections. Semin Perinatol 1983, 7(1):31-42.
• [23]Antoine P, Varner V, Carville A, Connole M, Marchant A, Kaur A: Postnatal acquisition of primary rhesus cytomegalovirus infection is associated with prolonged virus shedding and impaired CD4+ T lymphocyte function. J Infect Dis 2014, 210(7):1090-1099.
• [24]Yan H, Koyano S, Inami Y, Yamamoto Y, Suzutani T, Mizuguchi M, Ushijima H, Kurane I, Inoue N: Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children. Arch Virol 2008, 153(4):667-674.
• [25]Murph JR, Bale JF, Murray JC, Stinski MF, Perlman S: Cytomegalovirus transmission in a Midwest day care center: possible relationship to child care practices. J Pediatr 1986, 109:35-39.
• [26]Bello C, Whittle H: Cytomegalovirus infection in Gambian mothers and their babies. J Clin Pathol 1991, 44(5):366-369.
• [27]Berntsson M, Dubicanac L, Tunback P, Ellstrom A, Lowhagen GB, Bergstrom T: Frequent detection of cytomegalovirus and EpsteinBarr virus in cervical secretions from healthy young women. Acta Obstet Gynecol Scand 2013, 92(6):706-710.
• [28]Cannon MJ, Westbrook K, Levis D, Schleiss MR, Thackeray R, Pass RF: Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prev Med 2012, 54(5):351-357.
• [29]Stowell JD, Forlin-Passoni D, Radford K, Bate SL, Dollard SC, Bialek SR, Cannon MJ, Schmid DS: Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands. Appl Environ Microbiol 2014, 80(2):455-461.
• [30]Red Book: 2012 Report of the Committee on Infectious Diseases. 29th edition. American Academy of Pediatrics, Elk Grove Village, IL; 2012.
• [31]Perinatal Viral and Parasitic Infections. ACOG Practice Bulletin 20. ACOG, Washington, DC; 2000.
• [32]Adler SP: Screening for cytomegalovirus during pregnancy. Infect Dis Obstet Gynecol 2011, 2011:1-9.