Jennifer A. Unger

The emergence of Clostridium difficile infection among peripartum women: a case-control study of a C. difficile outbreak on an obstetrical service.

Objective. An outbreak of 20 peripartum Clostridium difficile infections (CDI) occurred on the obstetrical service at the University of Washington Medical Center (UWMC) between April 2006 and June 2007. In this report, we characterize the clinical manifestations, describe interventions that appeared to reduce CDI, and determine potential risk factors for peripartum CDI. Methods. An investigation was initiated after the first three peripartum CDI cases. Based on the findings, enhanced infection control measures and a modified antibiotic regimen were implemented. We conducted a case-control study of peripartum cases and unmatched controls. Results. During the outbreak, there was an overall incidence of 7.5 CDI cases per 1000 deliveries. Peripartum CDI infection compared to controls was significantly associated with cesarean delivery (70% versus 34%; P = 0.03 ), antibiotic use (95% versus 56%; P = 0.001), chorioamnionitis (35% versus 5%; P = 0.001), and the use of the combination of ampicillin, gentamicin, and clindamycin (50% versus 3%; P < 0.001 ). Use of combination antibiotics remained a significant independent risk factor for CDI in the multivariate analysis. Conclusions. The outbreak was reduced after the implementation of multiple infection control measures and modification of antibiotic use. However, sporadic CDI continued for 8 months after these measures slowed the outbreak. Peripartum women appear to be another population susceptible to CDI.

A Lifecycle Approach to HIV Prevention in African Women and Children

Effective biomedical and structural HIV prevention approaches are being implemented throughout sub-Saharan Africa. A “lifecycle approach” to HIV prevention recognizes the interconnectedness of the health of women, children and adolescents, and prioritizes interventions that have benefits across these populations. We review new biomedical prevention strategies for women, adolescents and children, structural prevention approaches, and new modalities for eliminating infant HIV infection, and discuss the implications of a lifecycle approach for the success of these methods. Some examples of the lifecycle approach include evaluating education and HIV prevention strategies among adolescent girls not only for their role in reducing risk of HIV infection and early pregnancy, but also to promote healthy adolescents who will have healthier future children. Similarly, early childhood interventions such as exclusive breastfeeding not only prevent HIV, but also contribute to better child and adolescent health outcomes. The most ambitious biomedical infant HIV prevention effort, Option B+, also represents a lifecycle approach by leveraging the prevention benefits of optimal HIV treatment for mothers; maternal survival benefits from Option B+ may have ultimately more health impact on children than the prevention of infant HIV in isolation. The potential for synergistic and additive benefits of lifecycle interventions should be considered when scaling up HIV prevention efforts in sub-Saharan Africa.

A Risk Assessment Tool for Identifying Pregnant and Postpartum Women Who May Benefit From Preexposure Prophylaxis

Background A human immunodeficiency virus (HIV) risk assessment tool for pregnant women could identify women who would most benefit from preexposure prophylaxis (PrEP) while minimizing unnecessary PrEP exposure. Methods Data from a prospective study of incident HIV among pregnant/postpartum women in Kenya were randomly divided into derivation (n = 654) and validation (n = 650) cohorts. A risk score was derived using multivariate Cox proportional hazards models and standard clinical prediction rules. Ability of the tool to predict maternal HIV acquisition was assessed using the area under the curve (AUC) and Brier score. Results The final risk score included the following predictors: having a male partner with unknown HIV status, number of lifetime sexual partners, syphilis, bacterial vaginosis (BV), and vaginal candidiasis. In the derivation cohort, AUC was 0.84 (95% confidence interval [CI], .72-.95) and each point increment in score was associated with a 52% (hazard ratio [HR], 1.52 [95% CI, 1.32-1.76]; P < .001) increase in HIV risk; the Brier score was 0.11. In the validation cohort, the score had similar AUC, Brier score, and estimated HRs. A simplified score that excluded BV and candidiasis yielded an AUC of 0.76 (95% CI, .67-.85); HIV incidence was higher among women with risk scores >6 than with scores ≤6 (7.3 vs 1.1 per 100 person-years, respectively; P < .001). Women with simplified scores >6 accounted for 16% of the population but 56% of HIV acquisitions. Conclusions A combination of indicators routinely assessed in antenatal clinics was predictive of HIV risk and could be used to prioritize pregnant women for PrEP.

Sexual Behavior and Vaginal Practices During Pregnancy and Postpartum: Implications for HIV Prevention Strategies.

Background: Understanding sexual behaviors and vaginal practices of pregnant and breastfeeding women in sub-Saharan Africa is critical to inform HIV prevention strategies during these periods. Methods: HIV-uninfected women presenting for antenatal care in western Kenya were enrolled and followed through 36 weeks postpartum. Sexual behavior and vaginal practices were ascertained by structured questionnaires. Logistic regression was used to assess correlates of unprotected sex, vaginal washing, and vaginal drying. Results: Among 1252 women enrolled, 78.4% were married (of whom 15.1% were in polygamous unions), 1.4% had a known HIV-infected partner, and 33.6% had a partner of unknown HIV status. At enrollment, 58.5% reported sex in the past month (94.3% unprotected) and 4.5% reported forced sex. Odds of unprotected sex at enrollment was >11-fold higher in married than in unmarried women (P < 0.001) and lower among women who reported partners of unknown HIV status or HIV-infected compared with HIV-uninfected partners. Median time to postpartum resumption of sex was 7 weeks (interquartile range 4–12). Prevalence of unprotected sex in the past week increased from 6.6% to 60.0% between 2 and 36 weeks postpartum (P < 0.001). Vaginal washing was reported by 60.1% of women at enrollment and prevalence remained stable postpartum; vaginal drying was reported by 17.9% at enrollment and decreased to 6.1% at 36 weeks postpartum (P < 0.001). Vaginal washing and drying were associated with forced sex. Conclusions: High rates of unknown partner HIV status, polygamy, and less frequent condom use among pregnant/postpartum women underscore the need for female-controlled HIV prevention interventions. Vaginal washing and drying may present challenges to microbicide use.

Evaluation of mHealth strategies to optimize adherence and efficacy of Option B+ prevention of mother-to-child HIV transmission: Rationale, design and methods of a 3-armed randomized controlled trial

BACKGROUND Lifelong antiretroviral therapy (ART) (Option B+) is recommended for all HIV-infected pregnant/postpartum women, but high adherence is required to maximize HIV prevention potential and maintain maternal health. Mobile health (mHealth) interventions may provide treatment adherence support for women during, and beyond, the pregnancy and postpartum periods. METHODS AND DESIGN We are conducting an unblinded, triple-arm randomized clinical trial (Mobile WACh X) of one-way short message service (SMS) vs. two-way SMS vs. control (no SMS) to improve maternal ART adherence and retention in care by 2years postpartum. We will enroll 825 women from Nairobi and Western Kenya. Women in the intervention arms receive weekly, semi-automated motivational and educational SMS and visit reminders via an interactive, human-computer hybrid communication system. Participants in the two-way SMS arm are also asked to respond to a question related to the message. SMS are based in behavioral theory, are tailored to participant characteristics through SMS tracks, and are timed along the pregnancy/postpartum continuum. After enrollment, follow-up visits are scheduled at 6weeks; 6, 12, 18, and 24months postpartum. The primary outcomes, virological failure (HIV viral load ≥1000copies/mL), maternal retention in care, and infant HIV infection or death, will be compared in an intent to treat analysis. We will also measure ART adherence and drug resistance. DISCUSSION Personalized and tailored SMS to support HIV-infected women during and after pregnancy may be an effective strategy to motivate women to adhere to ART and remain in care and improve maternal and infant outcomes.

Patient-Delivered Partner Treatment for Chlamydia, Gonorrhea, and Trichomonas Infection Among Pregnant and Postpartum Women in Kenya.

Background Patient-delivered partner treatment (PDPT) for sexually transmitted infections (STIs) increases rates of partner treatment and decreases reinfection, but has not been evaluated during pregnancy. Methods This prospective cohort was nested within a larger study of peripartum HIV acquisition. Participants with microbiologic diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis were screened for participation. Questionnaires were administered to determine PDPT acceptability and barriers. Women were reassessed at least 30 days to determine partner treatment and reinfection. Women whose partners did or did not receive PDPT were compared. Results One hundred twelve (22.2%) women in the parent cohort had a treatable STI; 78 within the PDPT study period, of whom 66 were eligible and 59 (89.3%) accepted PDPT. Fifty-one women had PDPT outcome data, 37 (73%) of whom reported partners treated with PDPT. Fourteen women (27%) refused or did not deliver partner treatment. Median age was 22 years (interquartile range, 20–26 years) and 88% were married. Compared with women who delivered PDPT, those who did not were more likely to have a partner living far away (23% vs. 0%, P = 0.004) and to report current intimate partner violence (14% vs. 0%, P = 0.02). Reported PDPT barriers included fear of partners anger/abuse (5%) and accusations of being STI source (5%). Conclusion Patient-delivered partner treatment was acceptable and feasible for pregnant/postpartum Kenyan women and may reduce recurrent STIs in pregnancy.

Mode of delivery and postpartum HIV-1 disease progression and mortality in a Kenyan cohort

BackgroundThere are limited data on the impact of cesarean section delivery on HIV-1 infected women in Sub-Saharan Africa. The purpose of this study was to assess the effect of mode of delivery on HIV-1 disease progression and postpartum mortality in a Kenyan cohort.MethodsA prospective cohort study was conducted in Nairobi, Kenya from 2000–2005. We determined changes in CD4+ counts, HIV-1 RNA levels and mortality during the first year postpartum between HIV-1 infected women who underwent vaginal delivery (VD), non-scheduled cesarean section (NSCS) and scheduled cesarean section (SCS) and received short-course zidovudine. Loess curves and multivariate linear mixed effects models were used to compare longitudinal changes in maternal HIV-1 RNA and CD4+ counts by mode of delivery. Kaplan Meier curves, the log rank test, and Cox proportional hazards regression were used to assess difference in mortality.ResultsOf 501 women, 405 delivered by VD, 74 delivered by NSCS and 22 by SCS. Baseline characteristics were similar between the VD and NSCS groups. Baseline antenatal CD4+ counts were lowest and HIV-1 RNA levels highest in the NSCS group but HIV-1 RNA levels were similar between groups at delivery. The rate of decline in CD4+ cells and rate of increase in HIV-1 RNA did not differ between groups. After adjusting for confounders, women who underwent NSCS had a 3.39-fold (95% CI 1.11, 10.35, P = 0.03) higher risk of mortality in the first year postpartum compared to women with VD.ConclusionsNon-scheduled cesarean section was an independent risk factor for postpartum mortality in HIV-1 positive Kenyan women. The cause of death was predominantly due to HIV-1 related infections, and not direct maternal deaths, however, this was not mirrored by differential changes in HIV-1 progression markers between the groups.

The Emergence ofClostridium difficileInfection among Peripartum Women: A Case-Control Study of aC. difficileOutbreak on an Obstetrical Service

Objective. An outbreak of 20 peripartum Clostridium difficile infections (CDI) occurred on the obstetrical service at the University of Washington Medical Center (UWMC) between April 2006 and June 2007. In this report, we characterize the clinical manifestations, describe interventions that appeared to reduce CDI, and determine potential risk factors for peripartum CDI. Methods. An investigation was initiated after the first three peripartum CDI cases. Based on the findings, enhanced infection control measures and a modified antibiotic regimen were implemented. We conducted a case-control study of peripartum cases and unmatched controls. Results. During the outbreak, there was an overall incidence of 7.5 CDI cases per 1000 deliveries. Peripartum CDI infection compared to controls was significantly associated with cesarean delivery (70% versus 34%; P = 0.03 ), antibiotic use (95% versus 56%; P = 0.001), chorioamnionitis (35% versus 5%; P = 0.001), and the use of the combination of ampicillin, gentamicin, and clindamycin (50% versus 3%; P < 0.001 ). Use of combination antibiotics remained a significant independent risk factor for CDI in the multivariate analysis. Conclusions. The outbreak was reduced after the implementation of multiple infection control measures and modification of antibiotic use. However, sporadic CDI continued for 8 months after these measures slowed the outbreak. Peripartum women appear to be another population susceptible to CDI.

Male partner circumcision associated with lower Trichomonas vaginalis incidence among pregnant and postpartum Kenyan women: a prospective cohort study

Objective Trichomonas vaginalis is the worlds most common curable STI and has implications for reproductive health in women. We determined incidence and correlates of T. vaginalis in an HIV-uninfected peripartum cohort. Methods Women participating in a prospective study of peripartum HIV acquisition in Western Kenya were enrolled during pregnancy and followed until 9 months post partum. T. vaginalis was assessed every 1–3 months using wet mount microscopy. Correlates of incident T. vaginalis were determined using Cox proportional hazards models. Results Among 1271 women enrolled, median age was 22 years (IQR 19–27) and gestational age was 22 weeks (IQR 18–26); most (78%) were married and had uncircumcised male partners (69%). Prevalent T. vaginalis was detected in 81 women (6%) at enrolment. Among women without T. vaginalis at enrolment, 112 had T. vaginalis detected during 1079 person-years of follow-up (10.4 per 100 person-years). After adjustment for socio-economic factors, male partner circumcision status, pregnancy status and other STIs, T. vaginalis incidence was higher during pregnancy than post partum (22.3 vs 7.7 per 100 person-years, adjusted HR (aHR) 3.68, 95% CI 1.90 to 7.15, p<0.001). Women with circumcised male partners had a 58% lower risk of incident T. vaginalis compared with women with uncircumcised partners (aHR 0.42, 95% CI 0.23 to 0.76, p=0.004). Employed women had lower risk of incident T. vaginalis than unemployed women (aHR 0.49, 95% CI 0.31 to 0.79, p=0.003); recent STI was associated with increased T. vaginalis risk (aHR 2.97, 95% CI 1.49 to 5.94, p=0.002). Conclusions T. vaginalis was relatively common in this peripartum cohort. Male circumcision may confer benefits in preventing T. vaginalis.

Sexually transmitted infections during pregnancy and subsequent risk of stillbirth and infant mortality in Kenya: a prospective study

Objectives We evaluated the relationship of sexually transmitted infections (STIs) and genital infections during pregnancy and subsequent risk for infant mortality and stillbirth. Methods This was a nested longitudinal analysis using data from a study of peripartum HIV acquisition in Kenya. In the parent study, HIV-uninfected women were enrolled during pregnancy and followed until 9 months postpartum. For this analysis, women who tested positive for HIV at any point, had a non-singleton pregnancy or a spontaneous abortion <20 weeks were excluded. At enrolment, laboratory methods were used to screen for bacterial vaginosis (BV), vaginal yeast, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Syphilis was diagnosed using rapid plasma reagin testing and genital ulcer disease (GUD) identified by clinical examination. Treatment of laboratory-confirmed STIs and syndromic management was provided per Kenyan national guidelines. Predictors of stillbirth and infant mortality were determined using logistic regression and Cox proportional hazards models. Results Overall, among 1221 women, 55% had STIs or genital infections detected: vaginal yeast (25%), BV (22%), TV (6%), CT (5%), NG (2%) and syphilis (1%). Among women with STIs/genital infections (n=592), 34% had symptoms. Overall, 19/1221 (2%) women experienced stillbirths. Among 1202 live births, 34 infant deaths occurred (incidence 4.0 deaths per 100 person-years, 95% CI 2.8 to 5.5). After adjustment for maternal age, education and study site, stillbirth was associated with maternal GUD (adjusted OR=9.19, 95% CI1.91 to 44.35, p=0.006). Maternal NG was associated with infant mortality (adjusted HR=3.83, 95% CI1.16 to 12.68, p=0.028); there was some evidence that maternal CT was associated with infant mortality. Stillbirth or infant mortality were not associated with other genital infections. Conclusions STIs and genital infections were common, frequently asymptomatic and some associated with stillbirth or infant mortality. Expediting diagnosis and treatment of STIs in pregnancy may improve infant outcomes.