460
Cytomegalovirus Infection in Sexually Active Adolescents Y. M. Sohn,* M. K. Oh, K. B. Balcarek, G. A. Cloud, and R. F. Pass
Departments of Pediatrics, Microbiology, and Biostatistics, University of Alabama at Birmingham School of Medicine
A variety of evidence indicates that cytomegalovirus (CMV) can be transmitted through sexual contact. The virus is shed in saliva, semen, and cervical secretions [1-5]. High rates of infection have been noted among groups with multiple sex contacts including women in venereal disease clinics and male homosexuals [6-8], and a high seroconversion rate, 37% per year, has been reported for women attending a sexually transmitted disease (STD) clinic [7]. In addition, CMV strains isolated from sex partners were identical when analyzed by restriction endonuclease techniques [9]. Because of the risk of congenital CMV, sexual transmission of CMV is of particular concern for women who are susceptible, sexually active, and likely to become pregnant. The high rate of teenage pregnancy in the United States suggests a potential for increasing problems with congenital CMV infection. To determine whether sexual activity is associated with CMV infection in teenaged girls, we studied adolescents attending a clinic that provides contraceptives and screens for STDs.
Materials and Methods Study population. Adolescent girls aged 12-18 years were enrolled between October 1986 and December 1988 from a special
Received 5 July 1990; revised 28 September 1990. Presented in part: 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, September 1989 (abstract 11). Written informed consent was obtained from participants. Grant support: National Institutes of Health (HD-I0699, HD-07300). Reprints or correspondence: Dr. Robert F. Pass, Department of Pediatrics, University of Alabama at Birmingham, 752 CHT, UAB Station, Birmingham, AL 35294. * Present address: Department of Pediatrics, Yonsei University School of Medicine, Seoul, South Korea. The Journal of Infectious Diseases 1991;163:460-463 © 1991 by The University of Chicago. All rights reserved. 0022-1899/91/6303-0005$01.00
clinic established to provide general health assessments and contraceptive counseling. This clinic serves a predominantly black, lowincome, urban population. Girls were invited to participate if the reason for their visit was a checkup rather than an illness. Those studied were interviewed for demographic data and sexual history and agreed to collection of specimens for STD screening and serum for antibody testing. Laboratory methods. Specimens from the genital tract were cultured for Chlamydia trachomatis and Neisseria gonorrhoeae, and wet mount slides were examined microscopically for Trichomonas vaginalis using methods that have been previously described [10]. The specimen for N. gonorrhoeae culture was obtained from the endocervix with a cotton-tipped applicator, inoculated onto modified Thayer-Martin medium, sealed in a plastic bag containing a C02generating tablet, and processed bythe JeffersonCounty (AL) Health Department Laboratory for identification of N. gonorrhoeae. Cultures of C. trachomatis were obtained from the endocervix using a sterile Dacron-tipped applicator that was placed in a tube of sucrosephosphate-bufferedtransport medium and cultured in cycloheximidetreated McCoy cell monolayers in 96-well tissue culture plates. After 48-72 h of incubation, inclusions were identified using a fluorescein-conjugated monoclonal antibody to C. trachomatis (Microtrak Culture Confirmation; Syva, Palo Alto, CA). T. vaginalis was identified in vaginal wet mounts as a motile, flagellated organism or by beating flagellar motion. Antibody to CMV was detected using a commercial enzyme immunoassay (CMV STAT; Whittaker M. A. Bioproducts, Walkersville, MD) or by the anticomplement immunofluorescence method [11]. Data analysis. Data from laboratory tests and interviews were assembled and analyzed using a VAX6210 computer and Statistical Analysis System software [12]. Frequencies of demographic and sexual history variables and STDs were determined for seropositive and seronegative girls. Rates were compared using x2 or Fisher's exact tests where appropriate. Odds ratios (OR) with 95 % confidence intervals (CI) for seropositivity were calculated. Sexual activity indicators (age at first sex ~13 years, >3 years of sexual activity, and >2 lifetime partners [total partners]) were used to define a composite variable based on the number of sexual activity indicators for each subject (0-3). Similarly, resultsof screening for N. gonorrhoeae,
Downloaded from http://jid.oxfordjournals.org/ at Penn State University (Paterno Lib) on August 11, 2014
To determine whether cytomegalovirus (CMV) infection in teenage girls is related to sexual activity, 254 girls 12-18 years old (mean, 15.8) attending a contraceptive counseling clinic were studied. Participants were screened for Chlamydia trachomatis, Neisseriagonorthoeae, and Trichomonasvaginalis, and serum antibody to CMv was determined. Demographic and sexual history data were collected by interview. The mean number of lifetime sex partners was 2.2; 173 (68%) were seropositive. Race, >3 years of sexual activity, and >2 lifetime sex partners were significant risk factors for CMV infection (odds ratios [OR], 1.8-4.7; P< .05). Using logistic regression analysis, a composite sexual activity variable was the most important risk factor for CMV infection (OR, 4.8; P = .003), followed by race (OR, 3.4; P = .004) and a sexually transmitted disease composite variable (OR, 2.4; P = .016). Sexual activity is an important risk factor for CMV infection in adolescent girls.
JID 1991;163 (March)
461
Sexual Transmission of CMV
C. trachomatis, and T. vaginalis were used to define a composite STD variable with each subjects having a score of 0-3. Multiple logistic regression analyses were done to determine the effect of multiple risk factors on the OR for CMV infection [13]. In the logistic analyses, the OR were calculated from the regression coefficient estimates. Age, race, gynecologic age, oral contraceptive use, the sexual activity composite variable (0 or 1 vs. 2 or 3), and the composite STD variable (0 vs. 1-3) were used in the logistic model.
tics, sexual activity indicators, and sexually transmitted diseases; subjects are grouped by CMV serologic status. P values and OR with 95 % CI are listed. Based on this univariate analysis, race, >3 years of sexual activity, and >2 lifetime sex partners all appeared to be risk factors for CMV infection, with respective OR of2.8, 4.7, and 1.8; P < .05 for all. Oral contraceptive use, however, was significantly more frequent among seronegative girls. Although age and age at first sex had OR >1, no statistically significant association with CMV infection was found. Similarly, OR for the sexually transmitted diseases ranged from 1.9 to 2.5, suggesting an association with CMV infection, but individually they did not achieve
Results
P< .05. The number of sexual activity variables for the seropositive and seronegative groups is shown in figure 1 as the percentage of each group who had 0, 1, 2, or 3 variables indicative of sexual activity «13 years at first sex, >3 years of sexual activity, and >2 lifetime sex partners). The seropositive girls had more of these risk indicators than did those seronegative. Of 161, 35 (21.7%) in the seropositive group had two or three indicators versus 5 (6.4%) of78 seronegative girls, P = .003. Figure 2 shows the percentage of seropositive and seronegative girls who had 0-3 STDs. The proportion ofCMV-infected subjects who had ~1 STD, 56 (33.1%) 169 was greater than for the seronegative group, 15 (18.5%) of 81, P = .02. The results of logistic regression analysis are shown in table 3 as adjusted OR. The model used to calculate adjusted OR included race, age, gynecologic age, sexual activity, STDs, and oral contraceptive use. Neither age nor gynecologic age were statistically significant in this model and are not shown. Oral contraceptives use again appeared to have a negative correlation with CMV infection. With control for other risk factors, the sexual activity composite variable had the strongest association with CMV infection (OR = 4.8; CI, 1.7-13.6), though black race (OR = 3.4; CI, 1.5-7.6) and the STD com-
Table 1. Characteristics of 254 adolescent girls attending a contraceptive counseling clinic. No. (%) or mean
Variable Race, black Age Gynecologic age Age at first sex Years sexual activity No. lifetime sex partners Oral contraceptive use None ~2 years >2 years Cytomegalovirus seropositive
214 (84) 15.8 ± 3.6 ± 14.1 ± 1.9 ± 2.2 ± 106 63 79 173
± 1 SD
1.4 1.5 1.5 1.1 1.4
(43) (25) (32) (68)
Table 2. Demographic features and sexual and sexually transmitted disease (STD) history in relation to cytomegalovirus serology at enrollment. % Variable Age ~ 15 years Race (black) Gynecologic age ~2 years Oral contraceptive use Sexual activity variables Age first sex, ~13 years Years sex activity, >3 No. lifetime partners, >2 STD variables Neisseria gonorrheae Chlamydia trachomatis Trichomonas vaginalis
%
seropositive seronegative (n = 173*) (n = 81*)
Odds ratio
95 % confidence interval
P
40 89 22 53
32 74 27 67
1.4 2.8 0.8 0.6
0.9, 1.9 1.7, 3.9 0.6, 1.1 0.3,0.9
.200 .002 .404 .042
34 11 37
27 3 24
1.4 4.7 1.8
0.9, 1.9 3.5,5.9 1.2,2.5
.300 .027 .045
9 21 14
4 12 6
2.5 1.9 2.5
0.5,4.5 1.0,2.8 1.0,4.0
.142 .084 .07
* Not all variables have complete data; n for each variable was
~92.4%
of total.
Downloaded from http://jid.oxfordjournals.org/ at Penn State University (Paterno Lib) on August 11, 2014
We studied 254 girls; characteristics of the study population are summarized in table 1. Most (84 %) were black; mean age was 15.8 years. The mean gynecologic age (years from menarche to study enrollment) was 3.6 ± 1.5 years. They averaged rv2 years of sexual activity and rv2 lifetime sex partners. Over half had used oral contraceptives. One hundred seventy-three (68%) had serum antibody to CMV. Table 2 shows frequencies for selected patient characteris-
462
Sohn et al.
~ Seropositive
100
•
Seronegative
80
c
Sexual activity composite* Black race STO composite t Oral contraceptive use
CD
o
~
Table 3. Adjusted odds ratios (OR) for cytomegalovirus infection with control for race, age, gynecologic age, sexual activity, sexually transmitted diseases (STDs), and oral contraceptive use by logistic regression analysis. Risk factor
_ 60 40 20
110 1991;163 (March)
* Analyzed as a dichotomous
Odds ratio 4.8 3.4 2.4 0.6
95% CI
1.7, 1.5, 1.2, 0.3,
13.6 7.6 4.8 1.0
p
.003 .004 .016 .064
variable, 0 or I indicator versus 2 or 3.
t Analyzed as a dichotomous variable, 0 versus I or more STDs.
o
o
3
Figure 1. Indicators of sexual activity (~13 years of age at sexual debut, >3 years of sexual activity, >2 lifetime partners) in relation to cytomegalovirus serologic status in adolescent girls. ~ Seropositive
100
•
Seronegative
80
C
60
CD 0
CD c,
40 20 0 0
1
2
3
Number of SrDs
Figure 2. Sexually transmitted diseases (STDs) versus cytomegalovirus serologic status. Girls were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Percentages of girls with 0-3 infections are shown.
posite (OR = 2.4; CI, 1.2-4.8) also remained statistically significant risk factors when confounding was controlled. Discussion We found a strong association between indicators of sexual activity and serologic evidence of CMV infection among young adolescent girls. More than 3 years of sexual activity and >2 lifetime sex partners were significant risk factors with univariate analysis, with respective OR of 4.7 and 1.8. Using logistic regression analysis to control for confounding, the presence of two or more sexual activity risk factors (young age at sexual debut, years of activity, number of lifetime partners) was the most important predictor of risk of CMV infection, with an OR of 4.8. Girls were screened for sexually transmitted infections. Although specific infections did not achieve statistical significance (P < .05) with univariate analysis, OR of 1.9-2.5 suggested an association with CMV infection. When grouped as a composite STD variable and examined by logis-
tic regression, STDs were a statistically significant risk factor for CMV infection. After controlling for confounding by age, gynecologic age, sexual activity, and STDs, race and oral contraceptive use were associated, respectively with increased risk (OR = 3.4) and decreased risk (OR = .6) of CMV infection. Although this study did not attempt to identify other potential risk factors, the higher rates of CMV infection among young black women could be due to exposures not related to sexual activity. Contact with young children is an important source of CMV infection for parents and day-care workers [14-16]. Thus more contact with young children either in early childhood or as a teenager providing care for younger family members could be a risk factor for CMV infection. Although we did not collect sufficient personal data to assess this exposure, none of our subjects was employed in child care and previous pregnancy was not associated with risk of CMV infection. As for the apparent protective effect of oral contraceptive use, we can offer no explanation at this time. Chandler et al. [17] observed a lower risk of CMV infection among women who had used barrier contraceptives. One could speculate that in the adolescent population, use of either type of contraceptive is a marker for better knowledge of the risks of sexual activity. Previous studies in women of childbearing age have also indicated a relationship between CMV infection and sexual activity. Jordan et al. [6] reported cervical shedding of CMV in 16 of 120 women seen because of suspected venereal disease and from none of 76 women receiving routine examinations. In the same study, both cervical shedding of virus and serum antibody were significantly more prevalent among women with past or active N. gonorrhoeae infection. Chandler et al. [17]studied 1129 pregnant women receiving prenatal care at the University of Washington and found a number of variables associated with serologic evidence of CMV infection, including greater number of lifetime sex partners, and infection with C trachomatis or T. vaginalis. In a similar study in women attending a sexually transmitted diseases clinic, Chandler et al. [7] again found a significant correlation between sexually transmitted infections (C trachomatis, N. gonorrhoeae, T. vaginalis, Mycoplasma hominis), greater number of lifetime sex partners, and CMV infection. The mean age of our study population was 1'\J5 years less than that of
Downloaded from http://jid.oxfordjournals.org/ at Penn State University (Paterno Lib) on August 11, 2014
1 2 Number of Sexual Activity Variables
JID 1991;163 (March)
Sexual Transmission of CMV
Acknowledgment Weacknowledge theexcellent assistance of theTeen Accent Clinic staff in enrolling patients and collecting specimens. References 1. Pass RF. Epidemiology and transmission of cytomegalovirus. J Infect Dis 1985;152:243-8. 2. Reynolds OW, Stagno S, Hosty TS, Tiller M, AlfordCA. Maternalcytomegalovirus excretion and perinatal infection. N Engl J Med 1973;289:1-5. 3. Nankervis GA, Kumar ML, Cox FE, Gold E. A prospective study of maternal cytomegalovirus infection and its effect on the fetus. Am J Obstet Gynecol 1984;149:435-40. 4. FaixRG, ZweigSE, Kummer JF, Moore0, LangOJ.Cytomegalovirusspecific cell-mediated immunity duringpregnancy in lowersocioeconomic class adolescents. J Infect Dis 1983;148:621-9.
5. LangOJ,Kummer JF. Cytomegalovirus in semen: observations inselected populations. J Infect Dis 1975;132:472-l 6. Jordan MC, Rousseau WE, NobleGR, Steward JA, Chin TO. Association of cervical cytomegaloviruses with venereal disease. N Engl J Med 1973;288:932-4. 7. Chandler SH, Holmes KK, Wentworth BB, GutmanLT. The epidemiology ofcytomegaloviral infection in women attending a sexually transmitted disease clinic. J Infect Dis 1985;152:597-605. 8. LangeM, KleinEB, Kornfield H, Cooper LZ, Grieco MH. Cytomegalovirus isolation from healthy homosexual men. JAMA 1984;252: 1908-10. 9. Handsfield HH, ChandlerSH, CaineVA, MeyersJD. Cytomegalovirus infection in sex partners: evidencefor sexual transmission. J Infect Dis 1985;151:344-8. 10. Oh MK, FeinsteinRA, Pass RF.Sexually transmitteddiseasesand sexual behaviorin urbanadolescentfemales attending a familyplanning clinic. J Adolesc Health Care 1988;9:67-71. 11. Stagno S, Pass RF, Britt Wl Cytomegalovirus. In: Schmidt NJ, Emmons RW, eds. Diagnostic procedures for viral, rickettsial and chlamydial infections. 6th ed. Washington, DC: American Public Health Association, 1989:321-78. 12. SAS user'sguide: statistics.Version 5 edition. Cary,NC: SAS Institute, 1985. 13. HalperinM, Blackwelder WC,VerterJI. Estimation of the multivariate risk function: a comparisonof the discriminantfunction and maximum likelihood approaches. J Chronic Dis 1971;24:125-58. 14. Pass RF, HuttoC, RicksR, CloudGA. Increasedrate of cytomegalovirus infection amongparents of children attendingday-care centers. N Engl J Med 1986;314:1414-8. 15. AdlerSP.Cytomegalovirus andchilddaycare:evidence foran increased infection rateamong daycareworkers, N EnglJ Moo1989;321:1290-6. 16. Pass RF, Hutto C, LyonMD, CloudG. Increasedrate of cytomegalovirus infection among day care center workers. Pediatr Infect Dis J 1990;9:465-70. 17. Chandler SH, Alexander ER, Holmes KK. Epidemiology of cytomegaloviral infection in a heterogeneous population of pregnant women. J Infect Dis 1985;152:249-56. 18. Hayes CD.Risking the future: adolescent sexuality, pregnancy andchildbearing. Vol 1. Report by the Panel on Adolescent Pregnancy and Childbearing of the National Research Council. Washington, DC: National Academy Press, 1987. 19. Henshaw SK, Van VortJ. Teenage abortion, birth and pregnancy statistics: an update. Fam Plann Perspect 1989;21:85-8.
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the STD clinic patients studied by Jordan et al. [6] and Chandler et al. [7] and nearly 10 years less than that of the prenatal patients reported by Chandler et al. [17]. A higher proportion of the girls we studied were black and more were of low socioeconomic status. Their mean number of lifetime sex partners was 2.2 compared with 22 for the STD clinic population [7]. It is remarkable that in a young adolescent study population with relatively limited sexual experience, correlation between CMV infection and sexual activity was so clear. Another consequence of adolescent sexual activity is pregnancy. It is estimated that 1 of 10 females aged 15-19 years in the United States becomes pregnant each year and that nearly a half million births per year are to women
Cytomegalovirus Infection in Sexually Active Adolescents Y. M. Sohn,* M. K. Oh, K. B. Balcarek, G. A. Cloud, and R. F. Pass
Departments of Pediatrics, Microbiology, and Biostatistics, University of Alabama at Birmingham School of Medicine
A variety of evidence indicates that cytomegalovirus (CMV) can be transmitted through sexual contact. The virus is shed in saliva, semen, and cervical secretions [1-5]. High rates of infection have been noted among groups with multiple sex contacts including women in venereal disease clinics and male homosexuals [6-8], and a high seroconversion rate, 37% per year, has been reported for women attending a sexually transmitted disease (STD) clinic [7]. In addition, CMV strains isolated from sex partners were identical when analyzed by restriction endonuclease techniques [9]. Because of the risk of congenital CMV, sexual transmission of CMV is of particular concern for women who are susceptible, sexually active, and likely to become pregnant. The high rate of teenage pregnancy in the United States suggests a potential for increasing problems with congenital CMV infection. To determine whether sexual activity is associated with CMV infection in teenaged girls, we studied adolescents attending a clinic that provides contraceptives and screens for STDs.
Materials and Methods Study population. Adolescent girls aged 12-18 years were enrolled between October 1986 and December 1988 from a special
Received 5 July 1990; revised 28 September 1990. Presented in part: 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, September 1989 (abstract 11). Written informed consent was obtained from participants. Grant support: National Institutes of Health (HD-I0699, HD-07300). Reprints or correspondence: Dr. Robert F. Pass, Department of Pediatrics, University of Alabama at Birmingham, 752 CHT, UAB Station, Birmingham, AL 35294. * Present address: Department of Pediatrics, Yonsei University School of Medicine, Seoul, South Korea. The Journal of Infectious Diseases 1991;163:460-463 © 1991 by The University of Chicago. All rights reserved. 0022-1899/91/6303-0005$01.00
clinic established to provide general health assessments and contraceptive counseling. This clinic serves a predominantly black, lowincome, urban population. Girls were invited to participate if the reason for their visit was a checkup rather than an illness. Those studied were interviewed for demographic data and sexual history and agreed to collection of specimens for STD screening and serum for antibody testing. Laboratory methods. Specimens from the genital tract were cultured for Chlamydia trachomatis and Neisseria gonorrhoeae, and wet mount slides were examined microscopically for Trichomonas vaginalis using methods that have been previously described [10]. The specimen for N. gonorrhoeae culture was obtained from the endocervix with a cotton-tipped applicator, inoculated onto modified Thayer-Martin medium, sealed in a plastic bag containing a C02generating tablet, and processed bythe JeffersonCounty (AL) Health Department Laboratory for identification of N. gonorrhoeae. Cultures of C. trachomatis were obtained from the endocervix using a sterile Dacron-tipped applicator that was placed in a tube of sucrosephosphate-bufferedtransport medium and cultured in cycloheximidetreated McCoy cell monolayers in 96-well tissue culture plates. After 48-72 h of incubation, inclusions were identified using a fluorescein-conjugated monoclonal antibody to C. trachomatis (Microtrak Culture Confirmation; Syva, Palo Alto, CA). T. vaginalis was identified in vaginal wet mounts as a motile, flagellated organism or by beating flagellar motion. Antibody to CMV was detected using a commercial enzyme immunoassay (CMV STAT; Whittaker M. A. Bioproducts, Walkersville, MD) or by the anticomplement immunofluorescence method [11]. Data analysis. Data from laboratory tests and interviews were assembled and analyzed using a VAX6210 computer and Statistical Analysis System software [12]. Frequencies of demographic and sexual history variables and STDs were determined for seropositive and seronegative girls. Rates were compared using x2 or Fisher's exact tests where appropriate. Odds ratios (OR) with 95 % confidence intervals (CI) for seropositivity were calculated. Sexual activity indicators (age at first sex ~13 years, >3 years of sexual activity, and >2 lifetime partners [total partners]) were used to define a composite variable based on the number of sexual activity indicators for each subject (0-3). Similarly, resultsof screening for N. gonorrhoeae,
Downloaded from http://jid.oxfordjournals.org/ at Penn State University (Paterno Lib) on August 11, 2014
To determine whether cytomegalovirus (CMV) infection in teenage girls is related to sexual activity, 254 girls 12-18 years old (mean, 15.8) attending a contraceptive counseling clinic were studied. Participants were screened for Chlamydia trachomatis, Neisseriagonorthoeae, and Trichomonasvaginalis, and serum antibody to CMv was determined. Demographic and sexual history data were collected by interview. The mean number of lifetime sex partners was 2.2; 173 (68%) were seropositive. Race, >3 years of sexual activity, and >2 lifetime sex partners were significant risk factors for CMV infection (odds ratios [OR], 1.8-4.7; P< .05). Using logistic regression analysis, a composite sexual activity variable was the most important risk factor for CMV infection (OR, 4.8; P = .003), followed by race (OR, 3.4; P = .004) and a sexually transmitted disease composite variable (OR, 2.4; P = .016). Sexual activity is an important risk factor for CMV infection in adolescent girls.
JID 1991;163 (March)
461
Sexual Transmission of CMV
C. trachomatis, and T. vaginalis were used to define a composite STD variable with each subjects having a score of 0-3. Multiple logistic regression analyses were done to determine the effect of multiple risk factors on the OR for CMV infection [13]. In the logistic analyses, the OR were calculated from the regression coefficient estimates. Age, race, gynecologic age, oral contraceptive use, the sexual activity composite variable (0 or 1 vs. 2 or 3), and the composite STD variable (0 vs. 1-3) were used in the logistic model.
tics, sexual activity indicators, and sexually transmitted diseases; subjects are grouped by CMV serologic status. P values and OR with 95 % CI are listed. Based on this univariate analysis, race, >3 years of sexual activity, and >2 lifetime sex partners all appeared to be risk factors for CMV infection, with respective OR of2.8, 4.7, and 1.8; P < .05 for all. Oral contraceptive use, however, was significantly more frequent among seronegative girls. Although age and age at first sex had OR >1, no statistically significant association with CMV infection was found. Similarly, OR for the sexually transmitted diseases ranged from 1.9 to 2.5, suggesting an association with CMV infection, but individually they did not achieve
Results
P< .05. The number of sexual activity variables for the seropositive and seronegative groups is shown in figure 1 as the percentage of each group who had 0, 1, 2, or 3 variables indicative of sexual activity «13 years at first sex, >3 years of sexual activity, and >2 lifetime sex partners). The seropositive girls had more of these risk indicators than did those seronegative. Of 161, 35 (21.7%) in the seropositive group had two or three indicators versus 5 (6.4%) of78 seronegative girls, P = .003. Figure 2 shows the percentage of seropositive and seronegative girls who had 0-3 STDs. The proportion ofCMV-infected subjects who had ~1 STD, 56 (33.1%) 169 was greater than for the seronegative group, 15 (18.5%) of 81, P = .02. The results of logistic regression analysis are shown in table 3 as adjusted OR. The model used to calculate adjusted OR included race, age, gynecologic age, sexual activity, STDs, and oral contraceptive use. Neither age nor gynecologic age were statistically significant in this model and are not shown. Oral contraceptives use again appeared to have a negative correlation with CMV infection. With control for other risk factors, the sexual activity composite variable had the strongest association with CMV infection (OR = 4.8; CI, 1.7-13.6), though black race (OR = 3.4; CI, 1.5-7.6) and the STD com-
Table 1. Characteristics of 254 adolescent girls attending a contraceptive counseling clinic. No. (%) or mean
Variable Race, black Age Gynecologic age Age at first sex Years sexual activity No. lifetime sex partners Oral contraceptive use None ~2 years >2 years Cytomegalovirus seropositive
214 (84) 15.8 ± 3.6 ± 14.1 ± 1.9 ± 2.2 ± 106 63 79 173
± 1 SD
1.4 1.5 1.5 1.1 1.4
(43) (25) (32) (68)
Table 2. Demographic features and sexual and sexually transmitted disease (STD) history in relation to cytomegalovirus serology at enrollment. % Variable Age ~ 15 years Race (black) Gynecologic age ~2 years Oral contraceptive use Sexual activity variables Age first sex, ~13 years Years sex activity, >3 No. lifetime partners, >2 STD variables Neisseria gonorrheae Chlamydia trachomatis Trichomonas vaginalis
%
seropositive seronegative (n = 173*) (n = 81*)
Odds ratio
95 % confidence interval
P
40 89 22 53
32 74 27 67
1.4 2.8 0.8 0.6
0.9, 1.9 1.7, 3.9 0.6, 1.1 0.3,0.9
.200 .002 .404 .042
34 11 37
27 3 24
1.4 4.7 1.8
0.9, 1.9 3.5,5.9 1.2,2.5
.300 .027 .045
9 21 14
4 12 6
2.5 1.9 2.5
0.5,4.5 1.0,2.8 1.0,4.0
.142 .084 .07
* Not all variables have complete data; n for each variable was
~92.4%
of total.
Downloaded from http://jid.oxfordjournals.org/ at Penn State University (Paterno Lib) on August 11, 2014
We studied 254 girls; characteristics of the study population are summarized in table 1. Most (84 %) were black; mean age was 15.8 years. The mean gynecologic age (years from menarche to study enrollment) was 3.6 ± 1.5 years. They averaged rv2 years of sexual activity and rv2 lifetime sex partners. Over half had used oral contraceptives. One hundred seventy-three (68%) had serum antibody to CMV. Table 2 shows frequencies for selected patient characteris-
462
Sohn et al.
~ Seropositive
100
•
Seronegative
80
c
Sexual activity composite* Black race STO composite t Oral contraceptive use
CD
o
~
Table 3. Adjusted odds ratios (OR) for cytomegalovirus infection with control for race, age, gynecologic age, sexual activity, sexually transmitted diseases (STDs), and oral contraceptive use by logistic regression analysis. Risk factor
_ 60 40 20
110 1991;163 (March)
* Analyzed as a dichotomous
Odds ratio 4.8 3.4 2.4 0.6
95% CI
1.7, 1.5, 1.2, 0.3,
13.6 7.6 4.8 1.0
p
.003 .004 .016 .064
variable, 0 or I indicator versus 2 or 3.
t Analyzed as a dichotomous variable, 0 versus I or more STDs.
o
o
3
Figure 1. Indicators of sexual activity (~13 years of age at sexual debut, >3 years of sexual activity, >2 lifetime partners) in relation to cytomegalovirus serologic status in adolescent girls. ~ Seropositive
100
•
Seronegative
80
C
60
CD 0
CD c,
40 20 0 0
1
2
3
Number of SrDs
Figure 2. Sexually transmitted diseases (STDs) versus cytomegalovirus serologic status. Girls were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Percentages of girls with 0-3 infections are shown.
posite (OR = 2.4; CI, 1.2-4.8) also remained statistically significant risk factors when confounding was controlled. Discussion We found a strong association between indicators of sexual activity and serologic evidence of CMV infection among young adolescent girls. More than 3 years of sexual activity and >2 lifetime sex partners were significant risk factors with univariate analysis, with respective OR of 4.7 and 1.8. Using logistic regression analysis to control for confounding, the presence of two or more sexual activity risk factors (young age at sexual debut, years of activity, number of lifetime partners) was the most important predictor of risk of CMV infection, with an OR of 4.8. Girls were screened for sexually transmitted infections. Although specific infections did not achieve statistical significance (P < .05) with univariate analysis, OR of 1.9-2.5 suggested an association with CMV infection. When grouped as a composite STD variable and examined by logis-
tic regression, STDs were a statistically significant risk factor for CMV infection. After controlling for confounding by age, gynecologic age, sexual activity, and STDs, race and oral contraceptive use were associated, respectively with increased risk (OR = 3.4) and decreased risk (OR = .6) of CMV infection. Although this study did not attempt to identify other potential risk factors, the higher rates of CMV infection among young black women could be due to exposures not related to sexual activity. Contact with young children is an important source of CMV infection for parents and day-care workers [14-16]. Thus more contact with young children either in early childhood or as a teenager providing care for younger family members could be a risk factor for CMV infection. Although we did not collect sufficient personal data to assess this exposure, none of our subjects was employed in child care and previous pregnancy was not associated with risk of CMV infection. As for the apparent protective effect of oral contraceptive use, we can offer no explanation at this time. Chandler et al. [17] observed a lower risk of CMV infection among women who had used barrier contraceptives. One could speculate that in the adolescent population, use of either type of contraceptive is a marker for better knowledge of the risks of sexual activity. Previous studies in women of childbearing age have also indicated a relationship between CMV infection and sexual activity. Jordan et al. [6] reported cervical shedding of CMV in 16 of 120 women seen because of suspected venereal disease and from none of 76 women receiving routine examinations. In the same study, both cervical shedding of virus and serum antibody were significantly more prevalent among women with past or active N. gonorrhoeae infection. Chandler et al. [17]studied 1129 pregnant women receiving prenatal care at the University of Washington and found a number of variables associated with serologic evidence of CMV infection, including greater number of lifetime sex partners, and infection with C trachomatis or T. vaginalis. In a similar study in women attending a sexually transmitted diseases clinic, Chandler et al. [7] again found a significant correlation between sexually transmitted infections (C trachomatis, N. gonorrhoeae, T. vaginalis, Mycoplasma hominis), greater number of lifetime sex partners, and CMV infection. The mean age of our study population was 1'\J5 years less than that of
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1 2 Number of Sexual Activity Variables
JID 1991;163 (March)
Sexual Transmission of CMV
Acknowledgment Weacknowledge theexcellent assistance of theTeen Accent Clinic staff in enrolling patients and collecting specimens. References 1. Pass RF. Epidemiology and transmission of cytomegalovirus. J Infect Dis 1985;152:243-8. 2. Reynolds OW, Stagno S, Hosty TS, Tiller M, AlfordCA. Maternalcytomegalovirus excretion and perinatal infection. N Engl J Med 1973;289:1-5. 3. Nankervis GA, Kumar ML, Cox FE, Gold E. A prospective study of maternal cytomegalovirus infection and its effect on the fetus. Am J Obstet Gynecol 1984;149:435-40. 4. FaixRG, ZweigSE, Kummer JF, Moore0, LangOJ.Cytomegalovirusspecific cell-mediated immunity duringpregnancy in lowersocioeconomic class adolescents. J Infect Dis 1983;148:621-9.
5. LangOJ,Kummer JF. Cytomegalovirus in semen: observations inselected populations. J Infect Dis 1975;132:472-l 6. Jordan MC, Rousseau WE, NobleGR, Steward JA, Chin TO. Association of cervical cytomegaloviruses with venereal disease. N Engl J Med 1973;288:932-4. 7. Chandler SH, Holmes KK, Wentworth BB, GutmanLT. The epidemiology ofcytomegaloviral infection in women attending a sexually transmitted disease clinic. J Infect Dis 1985;152:597-605. 8. LangeM, KleinEB, Kornfield H, Cooper LZ, Grieco MH. Cytomegalovirus isolation from healthy homosexual men. JAMA 1984;252: 1908-10. 9. Handsfield HH, ChandlerSH, CaineVA, MeyersJD. Cytomegalovirus infection in sex partners: evidencefor sexual transmission. J Infect Dis 1985;151:344-8. 10. Oh MK, FeinsteinRA, Pass RF.Sexually transmitteddiseasesand sexual behaviorin urbanadolescentfemales attending a familyplanning clinic. J Adolesc Health Care 1988;9:67-71. 11. Stagno S, Pass RF, Britt Wl Cytomegalovirus. In: Schmidt NJ, Emmons RW, eds. Diagnostic procedures for viral, rickettsial and chlamydial infections. 6th ed. Washington, DC: American Public Health Association, 1989:321-78. 12. SAS user'sguide: statistics.Version 5 edition. Cary,NC: SAS Institute, 1985. 13. HalperinM, Blackwelder WC,VerterJI. Estimation of the multivariate risk function: a comparisonof the discriminantfunction and maximum likelihood approaches. J Chronic Dis 1971;24:125-58. 14. Pass RF, HuttoC, RicksR, CloudGA. Increasedrate of cytomegalovirus infection amongparents of children attendingday-care centers. N Engl J Med 1986;314:1414-8. 15. AdlerSP.Cytomegalovirus andchilddaycare:evidence foran increased infection rateamong daycareworkers, N EnglJ Moo1989;321:1290-6. 16. Pass RF, Hutto C, LyonMD, CloudG. Increasedrate of cytomegalovirus infection among day care center workers. Pediatr Infect Dis J 1990;9:465-70. 17. Chandler SH, Alexander ER, Holmes KK. Epidemiology of cytomegaloviral infection in a heterogeneous population of pregnant women. J Infect Dis 1985;152:249-56. 18. Hayes CD.Risking the future: adolescent sexuality, pregnancy andchildbearing. Vol 1. Report by the Panel on Adolescent Pregnancy and Childbearing of the National Research Council. Washington, DC: National Academy Press, 1987. 19. Henshaw SK, Van VortJ. Teenage abortion, birth and pregnancy statistics: an update. Fam Plann Perspect 1989;21:85-8.
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the STD clinic patients studied by Jordan et al. [6] and Chandler et al. [7] and nearly 10 years less than that of the prenatal patients reported by Chandler et al. [17]. A higher proportion of the girls we studied were black and more were of low socioeconomic status. Their mean number of lifetime sex partners was 2.2 compared with 22 for the STD clinic population [7]. It is remarkable that in a young adolescent study population with relatively limited sexual experience, correlation between CMV infection and sexual activity was so clear. Another consequence of adolescent sexual activity is pregnancy. It is estimated that 1 of 10 females aged 15-19 years in the United States becomes pregnant each year and that nearly a half million births per year are to women
