[Show abstract][Hide abstract] ABSTRACT: To assess the volume of genital fluid collected for measuring the HIV-1 RNA level in cervicovaginal fluid, phosphate-buffered saline containing 10 mM LiCl was used. Thirty-eight women provided 275 cervicovaginal specimens. The estimated median volume of cervicovaginal fluid was 0.51 ml (interquartile range, 0.33, 0.69).
[Show abstract][Hide abstract] ABSTRACT: We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3-4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI -0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding.
AIDS research and human retroviruses 10/2010; 27(1):35-9. DOI:10.1089/aid.2010.0129 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether inadequate prenatal care is associated with increased risk of preterm birth among adolescents.
We selected a random sample of women under age 20 years with singleton pregnancies delivering in Washington State between 1995 and 2006. Multivariate logistic regression was used to assess the association between prenatal care adequacy (percent of expected visits attended, adjusted for gestational age) and preterm birth.
Of 30,000 subjects, 27,107 (90%) had complete data. Women without prenatal care had more than 7-fold higher risk of preterm birth (n = 84 [24.1%]; adjusted odds ratio [aOR], 7.4), compared with those attending 75-100% of recommended visits (n = 346 [3.9%]). Women with less than 25%, 25-49%, or 50-74% of expected prenatal visits were at significantly increased risk of preterm birth; risk decreased linearly as prenatal care increased (n = 60 [9.5%], 132 (5.9%], 288 [5%]; and aOR, 2.5, 1.5, and 1.3, respectively).
Inadequate prenatal care is strongly associated with preterm birth among adolescents.
American journal of obstetrics and gynecology 08/2010; 203(2):122.e1-6. DOI:10.1016/j.ajog.2010.03.001 · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We sought to determine if periconceptional exposure to agrichemicals was associated with the development of gastroschisis.
We conducted a retrospective, case-controlled study using Washington State Birth Certificate and US Geological Survey databases. Cases included all live-born singleton infants with gastroschisis. Distance between a woman's residence and site of elevated exposure to agrichemicals was calculated. Multivariate regression was used to estimate the association between surface water concentrations of agrichemicals and the risk of gastroschisis.
Eight hundred five cases and 3616 control subjects were identified. Gastroschisis occurred more frequently among those who resided <25 km from a site of high atrazine concentration (odds ratio, 1.6). Risk was related inversely to the distance between the maternal residence and the closest toxic atrazine site. In multivariate analysis, nulliparity, tobacco use, and spring conception remained significant predictive factors for gastroschisis.
Maternal exposure to surface water atrazine is associated with fetal gastroschisis, particularly in spring conceptions.
American journal of obstetrics and gynecology 03/2010; 202(3):241.e1-6. DOI:10.1016/j.ajog.2010.01.023 · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease in nonpregnant women. We investigated associations between cervical M genitalium, demographic and behavioral risk factors for sexually transmitted infection and preterm birth among low-income Peruvian women.
This case-control study, conducted at the Instituto Nacional Materno Perinatal, Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and 667 controls who delivered at >or=37 weeks. Within 48 hours after delivery, subjects underwent interviews, medical record review, and collection of cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by culture. Odds ratios and 95% confidence intervals were calculated for associations between M. genitalium, other genital infections and risk factors, and preterm birth. Multivariable logistic regression was used to adjust for potential confounders.
Cervical M. genitalium was detected in 3% of subjects and was significantly associated with C. trachomatis infection (P < 0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence interval: 1.2-5.0, P = 0.014), and marginally associated with T. vaginalis (P = 0.05). M. genitalium detection was also associated with younger maternal age (P = 0.003) but not with other risk factors for preterm birth. The association between cervical M. genitalium detection and preterm birth remained significant after adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis.
Cervical M. genitalium detection was independently associated with younger maternal age and preterm birth, suggesting that this organism may be an infectious correlate of spontaneous preterm birth.
[Show abstract][Hide abstract] ABSTRACT: Fastidious bacteria have been associated with bacterial vaginosis (BV) using PCR methods. We assessed the prevalence of these bacteria in HIV-1 infected women and their relationship with vaginal pH and shedding of HIV-1 RNA.
64 cervicovaginal lavage (CVL) samples were collected from 51 women. Vaginal microbiota were characterized using 8 bacterium-specific quantitative PCR assays.
Women with the fastidious bacteria Bacterial Vaginosis Associated Bacterium (BVAB) 1, 2, and 3 showed a trend to increased HIV-1 shedding (OR 2.59-3.07, P = .14-.17). Absence of Lactobacillus crispatus (P < .005) and presence of BVAB2 (P < .001) were associated with elevated vaginal pH. BVAB1, 2, and 3 were highly specific indicators of BV in HIV-infected women, with specificities of 89%-93%.
Fastidious bacteria (BVAB 1, 2, and 3) remain specific indicators of BV in HIV-infected women, and BVAB2 may contribute to the elevated vaginal pH that is a hallmark of this syndrome.
Infectious Diseases in Obstetrics and Gynecology 11/2009; 2009:236919. DOI:10.1155/2009/236919
[Show abstract][Hide abstract] ABSTRACT: Adolescent and young adult women in urban, socioeconomically disadvantaged areas are at high risk of contracting sexually transmitted infections (STIs). We assessed associations of Chlamydia trachomatis (CT) infection with both traditional STI risk factors, and partner and partnership-related factors among low-income women in Lima, Peru, by age group.
In a cross-sectional analysis of CT infection among 1290 postpartum women, cervical swabs were collected for CT polymerase chain reaction (PCR) within 48 h after delivery, and a structured interview was completed. Multivariate logistic regression was used to evaluate risk factors for CT, with separate models stratified by age: adolescents (12-19 years), young women (20-24 years), and older women (>or=25 years).
CT was detected in 9.6% of adolescents, 9.0% of young women, and 5.4% of older women (p = 0.03). Among adolescents, history of drug use (odds ratio [OR] = 5.62, 95% confidence interval [CI] 1.03-30.6) and short duration of current partnership (OR = 2.6, 95% CI 1.14-5.93) were the strongest predictors of CT infection. Among young women, younger age at coitarche (OR = 0.74 for each year older, 95% CI 0.60-0.91) and low income (OR = 2.40, 95% CI 1.04-5.55) were associated with CT, while self-report of ever using condoms was protective (OR = 0.22, 95% CI 0.08-0.61). Among older women, only younger age at coitarche was related to CT (OR = 0.85, 95% CI 0.75-0.97).
Risk factors for CT among women in Lima, Peru, differed for adolescents, young women, and older women, which may reflect differences in biology and/or immunology of CT as well as variability in the occurrence of specific risk behaviors by age group.
Journal of Women's Health 08/2009; 18(9):1419-24. DOI:10.1089/jwh.2008.1069 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is widespread recognition of the potential promise of vaginal microbicides as a tool to combat global human immunodeficiency virus/acquired immunodeficiency syndrome and sexually transmitted infections epidemics, and candidate product development has maintained a rapid pace in recent years; however, rectal microbicide development has received less attention. As it is likely that commercial products developed for vaginal use will also be used rectally, there is a clear need to assess the safety and efficacy of candidate microbicide products specifically in the rectal compartment.
We have developed a standardized protocol for preclinical rectal safety and (chlamydial) efficacy assessment of topical microbicide candidates in a nonhuman primate model. We evaluated a total of 12 test compounds for rectal safety (via rectal pH, microflora, and rectal lavage) and 1 compound for efficacy against rectal chlamydial infection.
In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the rectal environment. We also outline the specific criteria used to recommend products move into preclinical rectal efficacy trials or be recommended for reformulation to the product developer. In summary, we observed significant adverse effects in 2 products. The single product that underwent efficacy evaluation was not observed to be protective against rectal chlamydial infection.
A preclinical safety and efficacy model is critical to promoting rectal microbicide development, which will ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.
[Show abstract][Hide abstract] ABSTRACT: A woman's partner and the characteristics of their partnership can play an important role in the health of her pregnancy. Yet, with the notable exception of intimate partner violence, there has been little previous research addressing the associations between partner- or partnership-related factors and birth outcomes. This analysis tested the hypothesis that risk factors related specifically to partner or partnership characteristics increased the risk for preterm birth. Between 2003 and 2005, a total of 580 preterm cases (20-36 weeks gestational age at delivery) and 633 term controls (> or =37 weeks) were selected from women delivering at an obstetric hospital in Lima, Peru. Each woman completed a confidential, structured interview and provided biological specimens within 48 h after delivery. Multivariable logistic regression was used to assess associations between partner and partnership characteristics and preterm birth. After adjustment for behavioral, demographic, and obstetric risk factors, ever having had a partner with a history of drug use (aOR = 1.91, 95% CI 1.22-2.99), ever having had anal sex (aOR = 1.40, 95% CI 1.07-1.84), having a current partner with a history of visiting prostitutes (aOR = 1.69, 95% CI 1.22-2.33), and perceiving one's current partner as a "womanizer" (aOR = 1.34, 95% CI 1.02-1.77) were significantly associated with an elevated risk of preterm birth when tested in separate models. These four factors were then used to create a composite partnership risk score, which showed an increasing dose-response relationship with preterm birth risk (per additional partner risk factor: aOR = 1.31, 95% CI 1.16-1.49). These results highlight the importance of considering a broader set of risk factors for preterm birth, specifically those related to a woman's partner and partnership characteristics. Further research could clarify the specific mechanisms through which these partner and partnership characteristics may increase the risk of preterm birth.
Social Science & Medicine 04/2009; 68(8):1535-40. DOI:10.1016/j.socscimed.2009.02.027 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.
Vaginal samples were collected from 180 women (mean age 29.4 years, SD +/- 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at >or= 20% of tooth sites.
A Nugent score of 0-3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of Prevotella bivia (p < 0.001), and Prevotella disiens (p < 0.001). P. bivia, P. disiens, M. curtisii and M. mulieris (all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 x 104 cells) and a diagnosis of gingivitis was 3.9 for P. bivia (95% CI 1.5-5.7, p < 0.001) and 3.6 for P. disiens (95%CI: 1.8-7.5, p < 0.001), and a diagnosis of BV for P. bivia (odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and P. disiens (odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001).
Higher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. P. bivia and P. disiens may be of specific significance in a relationship between vaginal and gingival infections.
[Show abstract][Hide abstract] ABSTRACT: Background: HSV shedding at the genital mucosa increases the risk of shedding HIV. Suppression of HSV shedding with antivirals results in modest decreases in genital HIV shedding. CMV increases HIV replication both in vitro and in vivo, but the relative contribution of HSV and CMV genital shedding to genital HIV shedding remains unevaluated. Methods: 57 HIV+ American women collected genital swabs daily at home for 1-3 two-month periods for quantification of herpesvirus DNA. Cervicovaginal lavages (CVL) for quantification of HIV RNA and phlebotomy were performed by clinicians monthly. Results: 46 (100%) of 46 participants who contributed 4,732 specimens for HSV testing were HSV seropositive. 299 (6.3%) specimens were positive for HSV DNA. 32 (70%) women had >=1 positive HSV result. Among those who ever shed HSV, the mean frequency of shedding within subjects was 11.6% (range 0% - 57%, median 2.8%). 42 (91%) of 46 participants sampled for CMV quantification were CMV seropositive. 223 (4.6%) of 4,840 samples collected were positive for CMV DNA. 20 (43%) women had CMV detectable on >=1 day. Among those who ever shed CMV, shedding frequency was 13.2% (range 0% - 51%, median 0%). Overall, 24 (42%) of 57 women had HIV detected in CVL samples at >=1 visit. 18.5% of participant visits were positive for HIV shedding in CVL samples. Within women, the mean frequency of HIV shedding was 16%. In a model adjusting for plasma HIV RNA and ART use, shedding of each herpesvirus was independently associated with an increased risk of shedding HIV in CVL (incidence rate ratio for shedding HSV 1.6, 95% CI 1.2 - 2.2, p<0.01; and for shedding CMV 3.5, 95% CI 1.2 - 10.8, p=0.03). Conclusions: HSV and CMV each independently contribute to genital shedding of HIV. Antiviral suppression strategies aimed at both HSV and CMV could potentially optimize the reduction of HIV shedding in the genital tract.
Infectious Diseases Society of America 2008 Annual Meeting; 10/2008
[Show abstract][Hide abstract] ABSTRACT: The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.
We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the cervicovaginal environment. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer.
Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection.
The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.
[Show abstract][Hide abstract] ABSTRACT: Racial disparity in preterm birth is one of the most salient, yet least well-understood health disparities in the United States. The preterm birth disparity may be due to differences in how women experience their racial identity in light of neighborhood factors, psychosocial stress, or the prevalence of or response to genital tract infections such as bacterial vaginosis (BV). The latest research emphasizes a need to explore all these factors simultaneously. This cross-sectional study of parous women in King County, Washington, USA investigated the effects of household income, psychosocial stress, and neighborhood socioeconomic characteristics on risk of BV after accounting for known individual-level risk factors. Relevant demographic, socioeconomic, and medical data were linked to U.S. census socioeconomic data by geocoding subjects' residential addresses. It was found that having a low income was significantly associated with an increased prevalence of BV among African American but not White American women. A higher number of stressful life events was significantly associated with higher BV prevalence among both African American and White American women. However, perceived stress was not related to BV risk among either group of women. Among White American women, neighborhood socioeconomic status (SES) was univariately associated with increased BV prevalence by principal components analysis, but was no longer significant after adjusting for individual-level risk factors. No neighborhood SES effects were observed for African American women. These results suggest that both the effects of individual- and neighborhood-level risk factors for BV may differ importantly by racial group, and stressful life events may have physiological effects independent of perceived stress.
Social Science & Medicine 07/2008; 67(5):824-33. DOI:10.1016/j.socscimed.2008.05.017 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The persistent racial disparity in preterm birth (PTB)remains one of the most obvious yet poorly understood health disparities in the United States, and current evidence suggests that maternal stress, infection and inflammation may play an important role in the etiology of PTB. In this context, we assessed the complex relationships among racial identity; socioeconomic status (SES); psychosocial factors; and serum C-reactive protein (CRP), an inflammatory biomarker, among parous women in King County, WA. African-American women consistently reported a higher number of stressful life events than white American women (4.6 vs. 2.9, p < 0.001), as well as slightly higher levels of perceived stress and lower social support (24.7 vs. 22.2, p = 0.011, and 3.4 vs. 3.6, p = 0.06, respectively). In the multivariate analysis, African-American race, low-income status and their interaction were all independently associated with CRP; when further adjusted for proximal psychosocial, behavioral and infectious factors, race and income associations were significantly reduced. Stressful life events score was the single best proximal predictor of CRP levels (beta = 0.07 per event,p < 0.001), while perceived stress and social support were not significantly related to CRP. These results support the hypothesis that differences in CRP by racial identity and income may be mediated by differences in proximal risk factors, including stressful life events and health behaviors such as smoking. Objective life event stressors may be important to consider in future studies investigating a potential inflammatory etiology for preterm birth.
Journal of the National Medical Association 05/2008; 100(5):540-6. · 0.96 Impact Factor