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Association of Bacterial Vaginosis With Chlamydia and Gonorrhea Among


Women in the U.S. Army

Article  in  American Journal of Preventive Medicine · May 2017


DOI: 10.1016/j.amepre.2016.09.016

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RESEARCH ARTICLE

Association of Bacterial Vaginosis With Chlamydia and


Gonorrhea Among Women in the U.S. Army
Christian T. Bautista, MSc, MPH,1 Eyako K. Wurapa, MD, MTM&H,2 Warren B. Sateren, MPH, MBA,2
Sara M. Morris, PhD,1 Bruce P. Hollingsworth, PhD,1 Jose L. Sanchez, MD, MPH3

Introduction: Bacterial vaginosis (BV) is a common vaginal condition in women of reproductive


age, which has been associated with Chlamydia trachomatis and Neisseria gonorrhoeae among
commercial sex workers and women attending sexually transmitted infection clinics. Pathogen-
specific associations between BV and other sexually transmitted infections among U.S. military
women have not been investigated.
Methods: A population-based, nested case-control study was conducted of all incident chlamydia
and gonorrhea cases reported to the Defense Medical Surveillance System during 20062012. Using
a density sampling approach, for each chlamydia or gonorrhea case, 10 age-matched (⫾1 year)
controls were randomly selected from those women who were never diagnosed with these infections.
Incidence rate ratios were estimated using conditional logistic regression. Statistical analysis was
carried out in December 2015.
Results: A total of 37,149 chlamydia cases and 4,987 gonorrhea cases were identified during the
study period. Antecedent BV was associated with an increased risk of subsequent chlamydia
(adjusted incidence rate ratio¼1.51; 95% CI¼1.47, 1.55) and gonorrhea (adjusted incidence rate
ratio¼2.42; 95% CI¼2.27, 2.57) infections. For every one additional episode of BV, the risk of
acquiring chlamydia and gonorrhea infections increased by 13% and 26%, respectively. A
monotonic doseresponse relationship was also noted between antecedent BV and subsequent
chlamydia and gonorrhea infection. In addition, an effect modification on the additive scale was
found between BV and African-American race for gonorrhea, but not for chlamydia.

Conclusions: Among U.S. Army women, antecedent BV is associated with an increased risk of
subsequent chlamydia and gonorrhea infection.
Am J Prev Med 2017;52(5):632–639. & 2016 American Journal of Preventive Medicine. Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION New or multiple male sexual partners have been


associated with BV.4 Lower age at first intercourse, past

B
acterial vaginosis (BV) is a common vaginal
pregnancy, commercial sex work, and vaginal douching
condition characterized by gray/white, thin, and
malodorous discharge.1 BV is associated with the
replacement of normal vaginal lactobacilli by an over- From the 1Faculty of Health and Medicine, Lancaster University, Lancaster,
growth of vaginal anaerobes or Gram-negative bacteria United Kingdom; 2Walter Reed Army Institute of Research, Silver Spring,
(e.g., Gardnerella vaginalis), which causes an imbalance Maryland; and 3Armed Forces Health Surveillance Branch, Public Health
Division, Defense Health Agency, Silver Spring, Maryland
in the vaginal microflora with a resulting discharge. The Address correspondence to: Christian T. Bautista, MSc, MPH, Faculty of
BV prevalence varies substantially between countries Health and Medicine, Lancaster University, Bailrigg, Lancaster LA1 4YG,
worldwide.2 In the U.S., BV is more frequently reported Lancaster, United Kingdom. E-mail: cbautistat@gmail.com, m.bautista@
lancaster.ac.uk.
among African-American and Hispanic women than 0749-3797/$36.00
white women.3 http://dx.doi.org/10.1016/j.amepre.2016.09.016

632 Am J Prev Med 2017;52(5):632–639 & 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Bautista et al / Am J Prev Med 2017;52(5):632–639 633
5–8
are also linked to BV. Since the work of Leopold and 9 2012, were selected. For case findings, the ICD-9 was applied. For
Gardner and Dukes in the 1950s,10 the etiologic agent of chlamydia cases, the set ICD-9 codes were 099.41 or 099.5, and for
gonorrhea cases, the set ICD-9 codes were 098.0x, 098.1x, 098.4x,
BV has not been established, and there is debate on
or 098.8x. Using a density sampling approach,24 a random sample
whether BV constitutes a sexually transmitted infection of ten controls composed of women without a chlamydia or
(STI).11 However, it is also possible that BV is a sexually gonorrhea diagnosis at the time of diagnosis for the case were
enhanced disease.6 matched to each case on age (⫾1 year). Ten controls per case were
Data indicate that BV is a risk factor for the acquisition chosen to increase the statistical precision of the estimates.25
of pathogens such as HIV, herpes simplex virus Type 2, A BV diagnosis was based on the ICD-9-CM code 616.10
human papillomavirus, Chlamydia trachomatis, and (vaginitis and vulvovaginitis, unspecified) in either the first or the
Neisseria gonorrhoeae.12–17 For example, one cohort second diagnostic position of an outpatient or inpatient encounter
medical record from DMSS, prior to the diagnosis date of
study conducted among non-pregnant women found
chlamydia or gonorrhea. Because recurrent BV episodes are
that those with BV had a 1.8- and 1.9-fold increased risk frequent and there is no accepted definition of recurrence,26 an
for gonorrhea and chlamydia, respectively.18 A secondary episode of recurrent BV was defined as one where a subsequent
data analysis of the Project Protect clinical trial indicated diagnosis took place Z30 days from the previously diagnosed BV
that women with a high BV severity had a 2.7-fold episode. This criterion was based on the recommendations given
increased risk of acquiring an STI.19 by the Centers for Disease Control and Prevention BV Working
According to the Armed Forces Health Surveillance Group meta-analysis and synthesis report.3
Center, from 2000 through 2012, a total of 87,462
chlamydia and 11,403 gonorrhea cases were reported Measures
among military women.20 Chlamydia and gonorrhea rates Demographic variables, including race, education, marital status,
region of birth, rank, and years in service, were extracted from
are higher in military than civilian women. This difference DMSS. These were defined as race/ethnicity (white, African
may be due to the high prevalence of risky sexual practices American, Hispanic, and other), education (no high school, high
among the predominantly younger military women. How- school, and some college or higher), marital status (single, married,
ever, it might also be the result of a screening effect, as and other), rank (lower enlisted [E1E4], higher enlisted E5E9],
women undergo routine annual screening for STIs. and officers), and years of service (r1, 23, and Z4). Geographic
The relationship between BV and STIs has not been region or residence (birth) was classified into four regions (West,
examined among military women. Thus, this study Midwest, Northeast, and South).
sought to determine whether antecedent BV was asso-
ciated with subsequent chlamydia or gonorrhea infec- Statistical Analysis
The prevalence of BV among cases and controls was compared
tion, with special attention paid to Hispanic women, a
using the CochranMantelHaenszel test. To analyze individual
minority group not previously evaluated. This study also matched case-control data, conditional logistic regression was used
analyzed the role of the number of episodes of BV on STI to estimate the incidence rate ratios with 95% CIs to determine the
risk, as a doseresponse relationship has not previously association between BV and chlamydia and gonorrhea infection.
been studied. The identification of BV as risk factor for Separate regression models were performed for each variable
the transmission of these infections has potential impli- category. In addition to analyzing BV as a binary variable, BV
cations for prevention efforts in the U.S. military. was treated as a categorical variable to conduct a doseresponse
relationship analysis. An effect modification analysis on the
additive scale was conducted to determine whether the effect of
BV on chlamydia or gonorrhea infection differed by race/ethnicity.
METHODS For analysis, the synergy and the relative excess risk due to
interaction [RERI] measures were calculated. Synergy equal to one
Data Sample
and RERI equal to zero indicate there is no departure from
Study data were obtained from the Defense Medical Surveillance
additivity.25
System (DMSS); details about this surveillance system have been
All p-values were two-sided and were considered statistically
published elsewhere.21 Briefly, DMSS is the central repository of
significant if po0.05. Analyses were carried out in December 2015
medical surveillance data for the U.S. Armed Forces. This rela-
using Stata, version 14.0.
tional database contains information on personnel demographics,
The study was approved by scientific review and IRBs at
reportable diseases, deployments, and medical data for all active-
Lancaster University and the Walter Reed Army Institute of
duty personnel throughout their careers. DMSS data have pre-
Research.
viously been used to study HIV and herpes simplex virus Type 2
infections among U.S. military personnel.22,23
In this population-based, nested case-control study, all active RESULTS
duty women in the U.S. Army with a first-time diagnosis of
chlamydia or gonorrhea, in either the first or second diagnostic Chlamydia
position of an outpatient or inpatient, physician-based, diagnostic Between 2006 and 2012, a total of 37,149 chlamydia case
encounter reported between January 1, 2006 and December 31, patients were identified among U.S. Army women. Of

May 2017
634 Bautista et al / Am J Prev Med 2017;52(5):632–639
Table 1. BV Prevalence Among Chlamydia and Gonorrhea Cases and Matched Controls Among U.S. Army Females

Chlamydia Gonorrhea

Cases Controls Cases Controls

Feature BV % n/N BV % n/N BV % n/N BV % n/N


All participants 21.4 7,942/37,149 15.6 57,793/371,490 34.7 1,730/4,987 19.1 9,523/49,870
Race/ethnicity
White 16.5 2,440/14,827 12.2 23,623/193,291 26.1 297/1,136 14.2 3,608/25,096
African- 29.1 3,715/12,753 26.2 20,326/77,712 39.4 1,119/2,838 31.8 3,681/11,571
American
Hispanic 20.0 996/4,990 14.9 7,732/51,949 32.0 168/525 18.5 1,252/6,777
Othera 15.7 623/3,961 11.4 4,700/41,236 27.1 106/391 13.6 740/5,426
Education level
No high school 17.4 24/138 13.4 167/1,244 15.0 3/20 19.7 33/167
High school 20.5 6,758/32,929 14.9 46,727/312,692 34.1 1,521/4,456 18.4 7,602/41,330
College or 29.7 1,060/3,564 20.3 10,160/50,058 41.7 183/439 24.1 1,766/7,325
higher
Marital status
Single 16.6 4,211/25,371 11.2 26,653/238,865 28.2 919/3,257 13.8 4,181/30,369
Married 29.3 2,748/9,373 22.3 26,398/118,436 44.2 605/1,370 25.6 4,376/17,107
Otherb 40.9 976/2,387 33.7 4,712/13,993 57.1 201/352 40.6 960/2,367
Region of birthc
West 17.6 1,233/7,003 12.6 10,694/84,997 29.1 196/673 15.2 1,680/11,031
Midwest 19.3 1,021/5,279 13.8 7,995/57,716 35.3 211/598 16.6 1,246/7,519
Northeast 22.5 810/3,605 15.6 6,427/41,169 36.8 164/445 19.4 1,040/5,355
South 23.7 4,187/17,690 17.8 26,608/149,207 35.5 1,033/2,906 22.0 4,468/20,343
Military rank
Junior enlisted 17.7 5,586/31,579 12.1 35,149/289,502 30.2 1,239/4,107 14.6 5,420/37,029
Senior enlisted 46.0 2,091/4,544 35.3 18,884/53,429 59.4 458/771 38.8 3,470/8,931
Officers 25.8 265/1,026 13.2 3,760/28,559 30.3 33/109 16.2 633/3,910
Years of military service
r1 9.8 1,784/18,148 5.4 8,383/154,241 16.3 339/2,072 6.6 1,191/18,126
23 23.7 2,364/9,954 15.4 17,562/114,279 37.8 508/1,342 17.2 2,611/15,203
Z4 41.9 3,794/9,047 30.9 31,848/102,970 56.2 883/1,572 34.6 5,721/16,541
a
Other: American Indian/Alaskan Native, Asian/Pacific Islander, and others.
b
Other: Divorced, widowed, and others.
c
West (MT, WY, CT, NM, ID, UT, AZ, NV, WA, OR, CA, AK, and HI); Midwest (IL, IN, IA, KS, MI, MN, MO, OH, NE, ND, SD, and WI); Northeast (ME, NH, VT,
MA, RI, CT, NY, NJ, and PA); South (FL, GA, NC, SC, VA, WV, MD, DC, DE, AL, KY, MS, TN, AR, LA, OK, and TX).
BV, bacterial vaginosis.

these, 89% had high school education, 85% were in the with “other” marital status, women with college or higher
lower enlisted rank, 80% were aged o25 years, 68% were education, married personnel, and among African
single, 49% had at least 1 year of military service, 48% had Americans.
home of record in the South, and 34% were African After adjusting for covariates, BV was significantly
American. Among the 371,490 controls, 84% had high associated with chlamydia infection (incidence rate
school education, 78% were of lower enlisted rank, 64% ratio¼1.51; po0.001) (Table 2). These analyses also
were single, 41% had at least 1 year of military service, 40% showed that the association between BV and chlamydia
were from the South, and 21% were African American. was higher in women with junior enlisted rank, women
The prevalence of BV was higher among chlamydia who had r2 years of military service, women with single
cases than their controls (21.4% vs 15.6%, po0.001) marital status, and who were from the Northeast.
(Table 1). For both chlamydia cases and controls, the Interestingly, the association between BV and chlamydia
highest BV prevalences occurred among women with was higher among white women compared with African-
senior enlisted rank, those with 43 years of service, those American and Hispanic women.

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Bautista et al / Am J Prev Med 2017;52(5):632–639 635
Table 2. Crude and Adjusted Associations Between BV and Chlamydia and Gonorrhea Among U.S. Army Females

Chlamydia Gonorrhea

Feature IRR (95% CI) Adjusteda IRR (95% CI) IRR (95% CI) Adjusteda IRR (95% CI)
All participants 1.52 (1.47, 1.56) 1.51 (1.47, 1.55) 2.42 (2.26, 2.58) 2.42 (2.27, 2.57)
Race/ethnicity
White 1.46 (1.39, 1.54) 1.43 (1.36, 1.50) 2.28 (1.94, 2.68) 2.31 (1.96, 2.71)
African American 1.22 (1.16, 1.29) 1.24 (1.17, 1.31) 1.56 (1.41, 1.73) 1.58 (1.42, 1.75)
Hispanic 1.33 (1.20, 1.49) 1.36 (1.22, 1.52) 2.08 (1.53, 2.82) 2.12 (1.55, 2.90)
Otherb 1.33 (1.15, 1.53) 1.36 (1.18, 1.57) 2.65 (1.76, 3.99) 2.68 (1.78, 4.03)
Education level
No high school Undefinedc Undefinedc Undefinedc Undefinedc
High school 1.44 (1.40, 1.49) 1.50 (1.46, 1.55) 2.32 (2.16, 2.49) 2.44 (2.27, 2.62)
College or higher 1.68 (1.53, 1.84) 1.44 (1.31, 1.59) 2.20 (1.72, 2.81) 1.90 (1.47, 2.46)
Marital status
Single 1.63 (1.57, 1.69) 1.59 (1.53, 1.65) 2.71 (2.47, 2.97) 2.66 (2.42, 2.91)
Married 1.46 (1.38, 1.54) 1.44 (1.36, 1.51) 2.24 (1.97, 2.54) 2.23 (1.96, 2.54)
Otherd 1.38 (1.18, 1.61) 1.37 (1.17, 1.60) 1.68 (1.18, 2.41) 1.66 (1.15, 2.39)
Region of birthe
West 1.43 (1.32, 1.56) 1.42 (1.31, 1.55) 2.55 (1.99, 3.26) 2.59 (2.02, 3.32)
Midwest 1.51 (1.36, 1.68) 1.49 (1.34, 1.66) 2.90 (2.16, 3.90) 2.85 (2.10, 3.87)
Northeast 1.60 (1.40, 1.83) 1.52 (1.33, 1.75) 2.48 (1.75, 3.51) 2.41 (1.69, 3.43)
South 1.47 (1.41, 1.54) 1.48 (1.42, 1.54) 2.12 (1.93, 2.33) 2.14 (1.95, 2.36)
Military rank
Junior enlisted 2.20 (1.78, 2.71) 2.15 (1.74, 2.66) 2.37 (1.28, 4.37) 2.40 (1.29, 4.46)
Senior enlisted 1.47 (1.43, 1.52) 1.50 (1.45, 1.55) 2.46 (2.28, 2.66) 2.53 (2.34, 2.74)
Officers 1.56 (1.45, 1.67) 1.54 (1.43, 1.65) 2.22 (1.88, 2.63) 2.19 (1.85, 2.60)
Years of military service
r1 1.81 (1.71, 1.92) 1.82 (1.72, 1.93) 2.74 (2.36, 3.18) 2.74 (2.35, 3.19)
23 1.71 (1.61, 1.81) 1.72 (1.63, 1.83) 2.95 (2.56, 3.38) 2.95 (2.56, 3.40)
Z4 1.63 (1.56, 1.71) 1.61 (1.53, 1.69) 2.42 (2.16, 2.70) 2.38 (2.13, 2.68)
a
Adjusted IRR for race/ethnicity, marital status, and military rank.
b
Other: American Indian/Alaskan Native, Asian/Pacific Islander, and others.
c
Undefined IRR, zero or infinity.
d
Other: Divorced, widowed, and others.
e
West (MT, WY, CT, NM, ID, UT, AZ, NV, WA, OR, CA, AK, and HI); Midwest (IL, IN, IA, KS, MI, MN, MO, OH, NE, ND, SD, and WI); Northeast (ME, NH, VT,
MA, RI, CT, NY, NJ, and PA); South (FL, GA, NC, SC, VA, WV, MD, DC, DE, AL, KY, MS, TN, AR, LA, OK, and TX).
BV, bacterial vaginosis; IRR, incidence rate ratio.

When BV was treated as a continuous variable, for (95% CI¼1.29, 1.65), 1.95 (95% CI¼1.68, 2.26), and 2.07
every additional one episode of BV, the risk of chlamydia (95% CI¼1.83, 2.33), times higher, respectively.
infection increased by 13% (95% CI¼12%, 14%) com- The analysis did not detect an additive effect mod-
pared with women without BV. A similar estimate was ification between BV and chlamydia by race categorized
found after controlling for race/ethnicity, marital status, into two groups (African-American race and other race/
and military rank (data not shown). When BV was ethnic groups [white/Hispanic/other]; synergy¼1.02,
treated as a categorical predictor, a doseresponse 95% CI¼0.88, 1.90; RERI¼0.04, 95% CI¼0.24, 0.36).
relationship with chlamydia infection was found
(Figure 1). Women with one episode of BV had 1.45 Gonorrhea
(95% CI¼1.40, 1.50) times more risk of acquiring During the study period, a total of 4,987 gonorrhea case
chlamydia infection compared with women without patients were identified (Table 1). Of these, 89% had high
BV. Additionally, for women with two, three, four, five, school education, 82% were lower enlisted rank, 76%
and six or more episodes of BV, the risk of acquiring were aged o25 years, 65% were single, 58% were from
chlamydia compared with women without BV was 1.55 the South, 57% were African American, and 41% had at
(95% CI¼1.47, 1.64), 1.74 (95% CI¼1.61, 1.88), 1.46 least 1 year of military service. Among the 49,870

May 2017
636 Bautista et al / Am J Prev Med 2017;52(5):632–639

Figure 1. Associations for chlamydia infection by the Figure 2. Associations for gonorrhea infection by the num-
number of episodes of bacterial vaginosis among U.S. Army ber of episodes of bacterial vaginosis among U.S. Army
females. females.

controls, 83% had high school education, 74% were lower 4.55), 4.12 (95% CI¼3.14, 5.40), and 4.62 (95% CI¼3.73,
enlisted rank, 61% were single, 41% were from the South, 5.73), respectively.
36% had at least 1 year of military service, and 23% were Analyses also found that using an additive scale, race/
African American. ethnicity was a positive effect modifier for the relation-
The prevalence of BV was higher among gonorrhea ship between BV and gonorrhea (synergy¼1.29, 95%
cases than their controls (34.7% vs 19.1%, po0.001) CI¼1.05, 1.58; RERI¼1.80, 95% CI¼0.25, 3.34). This
(Table 1). Similar to the chlamydia results, the highest synergistic relationship indicates that the joint exposure
BV prevalences among gonorrhea cases and controls effect of BV and African-American race on gonorrhea
occurred among senior enlisted personnel, among was larger than the sum of the effect of African-American
women with Z4 years of service, African-American race on gonorrhea risk and of BV on gonorrhea risk.
women, those with other marital status, and among
women with college or higher education.
In a regression analysis, BV was significantly associated
with gonorrhea (incidence rate ratio¼2.42; po0.001). DISCUSSION
After controlling for race, marital status, and military Antecedent BV was associated with subsequent chlamy-
rank, the association between BV and gonorrhea was dia and gonorrhea infection among women in the U.S.
higher in women with the following characteristics: those Army. This represents the first large study to provide
with o4 years of military service, those from the Midwest, objective evidence of the role of the most common cause
single women, and those of other race/ethnic groups. of vaginal discharge, BV, on these two STIs. This
Analyses also revealed that for every additional epi- association was previously reported only among high-
sode of BV, the risk of gonorrhea infection increases 26% risk women in civilian populations.15–18
(95% CI¼23%, 28%, po0.001) compared with women Although it is difficult to estimate the exact prevalence of
without BV. This estimate was similar after controlling BV, as many women are asymptomatic, limited data on this
for race/ethnicity, marital status, and military rank (data vaginal condition indicates that among women entering mili-
not shown). When BV was analyzed as a categorical tary service in the U.S. Marine Corps during 19992000, a
predictor, the results showed a linear association between high prevalence was found among African-American (32%)
the number of episodes of BV and acquisition of and Hispanic women (30%).4 This finding is in agreement
gonorrhea infection (Figure 2). According to this with that observed in this study, in which African-American
doseresponse analysis, women with one episode of BV and Hispanic women had the highest BV prevalences.
had 1.98 (95% CI¼1.82, 2.15) times more risk of acquiring The prevalence of BV was two and three times higher
gonorrhea compared with women without BV. Addi- among African-American women with chlamydia or
tionally, compared with women without BV, the risk of gonorrhea compared with white women. This disparity,
acquiring gonorrhea among women with two, three, four, which has been reported in civilian studies,3,16 cannot be
five, and six or more episodes was 2.71 (95% CI¼2.41, explained by differences in sexual activity or sociodemo-
3.04), 3.22 (95% CI¼2.74, 3.79), 3.62 (95% CI¼2.87, graphic characteristics.27 It is possible that it is associated

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Bautista et al / Am J Prev Med 2017;52(5):632–639 637
with lifestyle factors that are more common among chlamydia and gonorrhea infection increased by 13% and
African-American women, such as vaginal douching. 26%, respectively. This increased risk was independent of
Vaginal douching, which causes a disequilibrium in the other covariates. To the best of the authors’ knowledge,
vaginal microflora, induces inflammation through either there is no evidence in the literature on the risk of STIs by
physical or chemical irritation, and therefore predisposes the number of episodes of BV. Although the basis for this
women to BV.28 On the other hand, it is hypothesized increased risk is not known, this study presents evidence
that differences in the composition of bacterial vaginal for the cumulative effect of BV on the risk for these
flora between whites and African Americans might infections.
explain this disparity,29 but there is no direct evidence This study also found a doseresponse relationship
of such a complex relationship. between antecedent BV and subsequent chlamydia and
This study found that women with BV were 1.5 and gonorrhea diagnosis. The shape of this relationship was
2.4 times more likely to have a subsequent chlamydia or monotonic, which indicates that the risk of these infec-
gonorrhea diagnosis when compared with their aged- tions increases with the number of episodes of BV. For
matched controls, respectively. These estimates were simplicity, the shape of the trend was analyzed descrip-
smaller for chlamydia, and higher for gonorrhea, when tively, and not using advanced statistical models, such as
compared with estimates from a large cohort study splines.32 This doseresponse relationship supports the
among 3,620 non-pregnant women aged 1544 years role of BV in the risk of STI acquisition. In addition to the
(hazard ratio for chlamydia¼1.9; hazard ratio for gon- observed strength of the association, an important com-
orrhea¼1.8).18 These findings are consistent with pre- ponent for disease causality, the presence of a dose
vious research suggesting that BV facilitates the response relationship has public health implications in
acquisition of these STIs. terms of disease prevention because it provides clues to the
This study also documents that among Hispanic biology underlying bacterialSTI relationship.
women, the relationship of BV with chlamydia or Effect modification analyses found a synergistic effect
gonorrhea infection was higher when compared with between BV and African-American race for gonorrhea,
African-American women. Data on the dynamics of STI but not for chlamydia. Although the mechanisms of this
transmission, including gonorrhea, among Hispanic effect remain unclear, biological factors, in addition to
women is limited in the military literature, despite the individual behavioral and social factors, may explain racial
fact that this minority group has increased its represen- disparities in STI acquisition.27–29 However, the nature of
tation in the U.S. military from 4% in 1981 to 13% in STIs among African Americans is complex, multifactorial
2013.30 Further studies are warranted in the military to in nature, and requires further individual and social
determine what individual, social, or biological factors networklevel behavioral research. This is the first study
contribute to the risk of STIs among Hispanic women. that suggests that African-American race modifies the
Analyses revealed that among single and enlisted association between BV and gonorrhea infection.
women, the association of BV with chlamydia or gonor- Taken together, this study provides additional evidence
rhea was stronger compared with those who were of a probable causal link between BV and chlamydia and
married or officers. Studies of active duty service women, gonorrhea infection. These conclusions are supported by
who are mostly single and young, report that they engage the strength of the associations, the temporal sequence of
in high-risk sexual behaviors (e.g., multiple sexual the associations, the consistency of findings with previous
partners, low condom use, and sex while under the studies, and a doseresponse relationship.
influence of drugs or alcohol).20,31 Additionally, among
young female recruits (aged 1721 years), BV has been
associated with having more than one sexual partner in Limitations
the past 3 months.4 Considering these findings, it is valid This study has some limitations. It is likely that the
to assume that high-risk sexual behaviors might explain reported number of women with BV was affected by the
the difference between single and married women. On limitations of use of ICD-9 codes as indicators of BV.
the other hand, in the U.S. Army, enlisted personnel are Therefore, it is probable that some women with BV were
predominantly young and unmarried. In this enlisted misclassified or had other conditions that also cause an
population, 71% of women were young (aged o25 years) inflammation or infection of the vagina, such as candi-
and unmarried. Consequently, this high percentage may diasis or noninfectious vaginitis. It was not possible to
explain, in part, the high association of BV with analyze behavioral risk data, given that this information
chlamydia and gonorrhea among the enlisted ranks. is not collected in DMSS. Further research should study
An important finding from this study was that for the influence of behavioral factors (e.g., sexual practices,
every one additional episode of BV, the risk of acquiring douching, use of condoms, and frequency of vaginal sex)

May 2017
638 Bautista et al / Am J Prev Med 2017;52(5):632–639
on the association of BV with chlamydia and gonorrhea 3. Koumans EH, Markowitz LE, Hogan V, CDC BV Working Group.
among military women. Indications for therapy and treatment recommendations for bacterial
vaginosis in nonpregnant and pregnant women: a synthesis of data.
Clin Infect Dis. 2002;35(suppl 2):S152–S172.
CONCLUSIONS 4. Fethers KA, Fairley CK, Hocking JS, Gurrin LC, Bradshaw CS. Sexual
risk factors and bacterial vaginosis: a systematic review and meta-
Among women in the U.S. Army, antecedent BV is analysis. Clin Infect Dis. 2008;47(11):1426–1435. http://dx.doi.org/
associated with an increased risk of subsequent chlamy- 10.1086/592974.
5. Yen S, Shafer MA, Moncada J, et al. Bacterial vaginosis in sexually
dia and gonorrhea infection. This finding is consistent experienced and non-sexually experienced young women entering the
with those observed amongst civilian populations where military. Obstet Gynecol. 2003;102(5 Pt 1):927–933. http://dx.doi.org/
BV has been reported to represent a strong risk factor for 10.1016/S0029-7844(03)00858-5.
both bacterial STIs. The doseresponse relationship 6. Smart S, Singal A, Mindel A. Social and sexual risk factors for bacterial
vaginosis. Sex Transm Infect. 2004;80(1):58–62. http://dx.doi.org/
between the number of episodes of BV and chlamydia
10.1136/sti.2003.004978.
or gonorrhea infection highlights the importance of BV 7. Verstraelen H, Verhelst R, Vaneechoutte M, Temmerman M. The
as a clinical risk factor, which can be considered epidemiology of bacterial vaginosis in relation to sexual behaviour.
“hypothesis generating” for further research in the field BMC Infect Dis. 2010;10:81. http://dx.doi.org/10.1186/1471-2334-
of STIs. The study also provides important evidence- 10-81.
8. Fethers KA, Fairley CK, Morton A, et al. Early sexual experiences and
based public health findings for U.S. military authorities risk factors for bacterial vaginosis. J Infect Dis. 2009;200(11):1662–
to develop prevention strategies such as sexual risk 1670. http://dx.doi.org/10.1086/648092.
reduction for female service members with BV in order 9. Leopold S. Heretofore undescribed organism isolated from the genito-
to reduce the acquisition of STIs. These results urinary system. U.S. Armed Forces Med. 1953;4(2):263–266.
10. Gardner HL, Dukes CD. Haemophilus vaginalis vaginitis: a newly
strengthen the literature that BV constitutes a predis-
defined specific infection previously classified non-specific vaginitis.
posing condition that increases the risk of both chlamy- Am J Obstet Gynecol. 1955;69(5):962–976. http://dx.doi.org/10.1016/
dia and gonorrhea infections. 0002-9378(55)90095-8.
11. Turovskiy Y, Noll KS, Chikindas ML. The aetiology of bacterial
vaginosis. J Appl Microbiol. 2011;110(5):1105–1128. http://dx.doi.org/
ACKNOWLEDGMENTS 10.1111/j.1365-2672.2011.04977.x.
12. Leppäluoto PA. Autopsy of bacterial vaginosis: a physiological entity
The authors would like to thank Dr. Angelia Cost, a senior rather than a contagious disease. Acta Obstet Gynecol Scand. 2008;87
managing epidemiologist at the Armed Forces Health Surveil- (5):578–579. http://dx.doi.org/10.1080/00016340802031049.
lance Branch, for Defense Medical Surveillance System data- 13. Mirmonsef P, Krass L, Landay A, Spear GT. The role of bacterial
base extraction and epidemiologic support for this study, and to vaginosis and trichomonas in HIV transmission across the female
Mr. Sebastian-Santiago for technical assistance. genital tract. Curr HIV Res. 2012;10(3):202–210. http://dx.doi.org/
This study was funded by the U.S. Armed Forces Health 10.2174/157016212800618165.
Surveillance Branch and its Global Emerging Infectious Surveil- 14. Nagot N, Quedraogo A, Defer MC, et al. Association between bacterial
vaginosis and Herpes simplex virus type-2 infection: implications for
lance section.
HIV acquisition studies. Sex Transm Infect. 2007;83(5):365–368. http:
The views expressed herein are those of the authors and do
//dx.doi.org/10.1136/sti.2007.024794.
not reflect the official policy or position of the Department of the 15. Brotman RM, Shardell MD, Gajer P, et al. Interplay between the
Army, Department of Defense, the U.S. Government, or any temporal dynamics of the vaginal microbiota and human papilloma-
listed organization. Some authors are employees of the U.S. virus detection. J Infect Dis. 2014;210(11):1723–1733. http://dx.doi.org/
government. This work was prepared as part of their official 10.1093/infdis/jiu330.
duties and, as such, there is no copyright to be transferred. This 16. Wiesenfeld HC, Hillier SL, Krohn MA, Landers DV, Sweet RL.
report was approved for publication by the U.S. Army Public Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and
Health Command. Chlamydia trachomatis infection. Clin Infect Dis. 2003;36(5):663–668.
Preliminary results from this study were presented at the 29th http://dx.doi.org/10.1086/367658.
European Conference on Sexually Transmitted Infections, 17. Gallo MF, Macaluso M, Warner L, et al. Bacterial vaginosis, gonorrhea,
poster #168, Barcelona, Spain, September 2426, 2015. and chlamydial infection among women attending a sexually trans-
mitted disease clinic: a longitudinal analysis of possible causal links.
No financial disclosures were reported by the authors of
Ann Epidemiol. 2012;22(3):213–220. http://dx.doi.org/10.1016/j.
this paper. annepidem.2011.11.005.
18. Brotman RM, Klebanoff MA, Nansel TR, et al. Bacterial vaginosis
assessed by gram stain and diminished colonization resistance to
REFERENCES incident gonococcal, chlamydial, and trichomonal genital infection. J
1. Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial Infect Dis. 2010;202(12):1907–1915. http://dx.doi.org/10.1086/657320.
vaginosis in the United States, 2001-2004; associations with symptoms, 19. Allsworth JE, Peipert JF. Severity of bacterial vaginosis and the risk of
sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34 sexually transmitted infection. Am J Obstet Gynecol. 2011;205(2):113.
(11):864–869. http://dx.doi.org/10.1097/OLQ.0b013e318074e565. http://dx.doi.org/10.1016/j.ajog.2011.02.060.
2. Kenyon C, Colebunders R, Crucitti T. The global epidemiology of 20. Armed Forces Health Surveillance Center. Sexually transmitted
bacterial vaginosis: a systematic review. Am J Obstet Gynecol. 2013;209 infections, active component, U.S. Armed Forces, 20002012. MSMR.
(6):505–523. http://dx.doi.org/10.1016/j.ajog.2013.05.006. 2013;20(2):5–10.

www.ajpmonline.org
Bautista et al / Am J Prev Med 2017;52(5):632–639 639
21. Rubertone MV, Brundage JF. The Defense Medical Surveillance 27. Royce RA, Jackson TP, Thorp JM Jr, et al. Race/ethnicity, vaginal flora
System and the Department of Defense serum repository: glimpses patterns, and pH during pregnancy. Sex Transm Dis. 1999;26(2):96–
of the future of public health surveillance. Am J Public Health. 2002;92 102. http://dx.doi.org/10.1097/00007435-199902000-00007.
(2):1900–1904. http://dx.doi.org/10.2105/AJPH.92.12.1900. 28. Brotman RM, Klebanoff MA, Nansel TR, et al. A longitudinal study of
vaginal douching and bacterial vaginosis: a marginal structural
22. Bautista CT, Sateren WB, Sanchez JL, et al. HIV incidence trends
among white and African-American active duty United States Army modeling analysis. Am J Epidemiol. 2008;168(2):188–196. http://dx.
doi.org/10.1093/aje/kwn103.
personnel (19862003). J Acquir Immune Defic Syndr. 2006;43(3):
29. Hickey RJ, Zhou X, Pierson JD, Ravel J, Forney LJ. Understanding vaginal
351–355. http://dx.doi.org/10.1097/01.qai.0000243051.35204.d0.
microbiome complexity from an ecological perspective. Transl Res.
23. Bautista CT, Singer DE, O’Connell RJ, et al. Herpes simplex virus type 2012;160(4):267–282. http://dx.doi.org/10.1016/j.trsl.2012.02.008.
2 and HIV infection among U.S. military personnel: implications for 30. Holder K. Post 9/11 women veterans. Proceedings of the Annual
health prevention programmes. Int J STD AIDS. 2009;20(9):634–637. Meeting of the Population Association of America; Apr 1517;2010.
http://dx.doi.org/10.1258/ijsa.2008.008413. Dallas, TX: Housing and Household Economic Statistics Division,
24. Richardson D. An incidence density sampling program for nested case- U.S. Census Bureau; 2010.
control analyses. Occup Environ Med. 2004;61:e59. http://dx.doi.org/ 31. Stahlman S, Javanbakht M, Cochran S, et al. Self-reported STIs and
10.1136/oem.2004.014472. sexual risk behaviors in the U.S. military: how gender influences risk.
Sex Transm Dis. 2014;41(6):359–364. http://dx.doi.org/10.1097/
25. Rothman KJ, Greenland S, Lash TL, eds. Modern Epidemiology. OLQ.0000000000000133.
Philadelphia, PA: Lippincott Williams & Wilkins, 2008.
32. Steenland K, Deddens JA. A practical guide to dose-response
26. Eschenbach DA. Bacterial vaginosis: resistance, recurrence, and/or analyses and risk assessment in occupational epidemiology. Epidemio-
reinfection? Clin Infect Dis. 2007;44(2):220–221. http://dx.doi.org/ logy. 2004;15(1):63–70. http://dx.doi.org/10.1097/01.ede.0000100287.
10.1086/509584. 45004.e7.

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