Richard H. Beigi

Teratogenic effects of the Zika virus and the role of the placenta

The mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis.

Economic Value of Seasonal and Pandemic Influenza Vaccination during Pregnancy

BACKGROUND The cost-effectiveness of maternal influenza immunization against laboratory-confirmed influenza has never been studied. The current 2009 H1N1 influenza pandemic provides a timely opportunity to perform such analyses. The study objective was to evaluate the cost-effectiveness of maternal influenza vaccination using both single- and 2-dose strategies against laboratory-confirmed influenza secondary to both seasonal epidemics and pandemic influenza outbreaks. METHODS A cost-effectiveness decision analytic model construct using epidemic and pandemic influenza characteristics from both the societal and third-party payor perspectives. A comparison was made between vaccinating all pregnant women in the United States versus not vaccinating pregnant women. Probabilistic (Monte Carlo) sensitivity analyses were also performed. The main outcome measures were incremental cost-effectiveness ratios (ICERs). RESULTS Maternal influenza vaccination using either the single- or 2-dose strategy is a cost-effective approach when influenza prevalence > or =7.5% and influenza-attributable mortality is > or =1.05% (consistent with epidemic strains). As the prevalence of influenza and/or the severity of the outbreak increases the incremental value of vaccination also increases. At a higher prevalence of influenza (> or =30%) the single-dose strategy demonstrates cost-savings while the 2-dose strategy remains highly cost-effective (ICER, < or =

Vaginal yeast colonization in nonpregnant women: a longitudinal study.

6787.77 per quality-adjusted life year). CONCLUSIONS Maternal influenza immunization is a highly cost-effective intervention at disease rates and severity that correspond to both seasonal influenza epidemics and occasional pandemics. These findings justify ongoing efforts to optimize influenza vaccination during pregnancy from an economic perspective.

Pelvic Inflammatory Disease and Tubo-ovarian Abscess

OBJECTIVE: We sought to investigate the prevalence and risk factors for vaginal yeast colonization over a 1-year period. METHODS: We conducted a longitudinal cohort study of 1,248 asymptomatic young women by collecting demographic and behavioral data at baseline, 4, 8, and 12 months. RESULTS: Seventy percent of women were colonized by vaginal yeast at one or more visits, but only 4% were colonized at all 4 visits. Using an adjusted generalized estimating equation model, factors associated with vaginal yeast colonization were marijuana use in the previous 4 months, depomedroxyprogesterone acetate use in the past 4 months, sexual intercourse in the previous 5 days, and concurrent colonization with lactobacilli and group B streptococcus. Symptoms of pruritus and vulvovaginal burning were associated with yeast colonization, but antifungal use was not. CONCLUSION: Recent sexual intercourse and use of injection contraceptives are risk factors for yeast colonization. Rates of antifungal use did not show an association with yeast colonization. The reporting of antifungal use by women lacking yeast colonization suggests that self-diagnosis is inaccurate. LEVEL OF EVIDENCE: II-2

Recommendations from the national vaccine advisory committee: Standards for adult immunization practice

Pelvic inflammatory disease (PID) is common infection among reproductive-aged women. The presentation ranges from acute severe illness to a more indolent and mild clinical picture. Attention has turned to subclinical PID as an important entity. The majority of the public health impact from PID comes from its attributable long-term sequelae, including tubal-factor infertility, ectopic pregnancy, and chronic pelvic pain. Tubo-ovarian abscess (TOA) represents a severe form of PID. Vigilance is required when caring for women who have PID to detect the presence of a TOA given the serious nature of the infection and the potential need for procedural intervention.

Pharmacokinetics of oseltamivir among pregnant and nonpregnant women

National Vaccine Advisory Committee The Advisory Committee on Immunization Practices (ACIP) makes recommendations for routine vaccination of adults in the United States.1 Standards for implementing the ACIP recommendations for adults were published by the National Vaccine Advisory Committee (NVAC) in 20032 and by the Infectious Diseases Society of America in 2009.3 In addition, NVAC published a report in 2012 outlining a pathway for improving adult immunization rates.4 While most of these documents included guidelines for immunization practice, recent changes in the practice climate for adult immunization necessitated an update of existing adult immunization standards. Some of these changes include expansion of vaccination services offered by pharmacists and other community immunization providers both during and since the 2009 H1N1 influenza pandemic; vaccination at the workplace; increased vaccination by providers who care for pregnant women; and changes in the health-care system, including the Affordable Care Act (ACA), which requires first-dollar coverage of ACIP-recommended vaccines for people with certain private insurance plans, or those who are beneficiaries of expanded Medicaid plans.5 The ACA first-dollar provision is expected to increase the number of adults who will be insured for vaccines. Other changes include expanding the inclusion of adults in state immunization information systems (IISs) (i.e., registries) and the Centers for Medicare & Medicaid Services Meaningful Use Stage 2 requirements, which mandate provider reporting of immunizations to registries, including reporting of adult vaccination in states where such reporting is allowed.6 For the purposes of this report, provider refers to any individual who provides health-care services to adult patients, including physicians, physician assistants, nurse practitioners, nurses, pharmacists, and other health-care professionals. While previous versions of the adult immunization standards have been published, recommendations for adult vaccination are published annually, and many health-care organizations have endorsed routine assessment and vaccination of adults, vaccination among adults continues to be low.7–15 Several barriers to adult vaccination include:

Influenza immunization in pregnancy: overcoming patient and health care provider barriers

We sought to delineate the pharmacokinetics (PK) of oseltamivir and its active metabolite oseltamivir carboxylate during pregnancy. Physiologic changes of pregnancy, including increased renal filtration and secretion, may increase the clearance of oseltamivir carboxylate. Sixteen pregnant women taking oseltamivir for prophylaxis or treatment of suspected/proven influenza infection were enrolled. Twenty-three nonpregnant reproductive-age females served as the control group. The primary PK endpoint was area under the plasma concentration time curve for oseltamivir carboxylate. Pregnancy did not alter the PK parameters of the parent compound, oseltamivir. However, for oseltamivir carboxylate the area under the plasma concentration time curve was significantly lower (P = .007) and the apparent clearance significantly higher (P = .006) in pregnant women compared with nonpregnant women. Pregnancy produces lower systemic levels of oseltamivir carboxylate. Increasing the dose and/or dosing frequency of oseltamivir during pregnancy may be necessary to achieve comparable exposure in pregnant and nonpregnant women.

Improving influenza vaccination rates in pregnancy through text messaging: a randomized controlled trial.

Seasonal influenza imparts disproportionate morbidity and death to pregnant women. Immunization against influenza is the most effective intervention to mitigate the burden of influenza disease during pregnancy; nevertheless, immunization rates remain suboptimal in this patient population. Therefore, there is a clear need for strategies to optimize influenza vaccination among pregnant women. We reviewed potential patient and health care provider barriers to influenza immunization and propose effective strategies for overcoming them.

Cytokines, Pregnancy, and Bacterial Vaginosis: Comparison of Levels of Cervical Cytokines in Pregnant and Nonpregnant Women with Bacterial Vaginosis

OBJECTIVE: To estimate whether text messages sent to ambulatory pregnant women could improve influenza vaccine uptake. METHODS: Obstetric patients at less than 28 weeks of gestation were enrolled in a randomized controlled trial from an academic centers outpatient clinic during two consecutive influenza seasons (2010–2011 and 2011–2012). Potential participants were excluded if they had already received that seasons influenza vaccine. Participants were randomized to receive 12 weekly text messages encouraging general pregnancy health (General) or general pregnancy health plus influenza vaccination (Flu). Study participants completed preintervention and postintervention surveys about preventive health beliefs. Influenza vaccine receipt was assessed using prenatal record review. The study was powered to detect a 55% increase in the vaccination rate in the intervention group. RESULTS: Two hundred sixteen women were enrolled, 204 of whom were available for intention-to-treat analysis (n=100 General, n=104 Flu). Participants were primarily African American (66%) with low educational attainment (90% equivalent to or less than high school education) and predominantly with either public or no insurance (88%). The overall influenza vaccination rate among participants was 32% with no difference between participants in the General (31% [n=31]) compared with Flu (33% [n=34]) groups (difference 1.7%, 95% confidence interval −11.1 to 14.5%). CONCLUSION: Text messaging prompts were not effective at increasing influenza vaccination rates among a low-income, urban, ambulatory obstetric population. Ongoing efforts are needed to improve vaccine uptake among pregnant women unsure about or unwilling to receive influenza vaccination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01248520. LEVEL OF EVIDENCE: I

Epidemiologic and Economic Effect of Methicillin-resistant Staphylococcus aureus in Obstetrics

BACKGROUND Pregnancy has been considered to be a time of relative immune compromise. Lower-genital-tract immune response appears to be influenced by pregnancy. The objective of this study was to compare, in pregnant versus nonpregnant women, endocervical proinflammatory-cytokine expression in response to bacterial vaginosis. METHODS Endocervical levels of interleukin (IL)-1 beta , IL-6, and IL-8 in 99 pregnant and 99 nonpregnant women, all with bacterial vaginosis and without concurrent sexually transmitted infections, were assessed by ELISA. Vaginal flora was characterized on the basis of quantitative vaginal cultures. RESULTS Women in the 2 groups differed with respect to smoking status and microbiological constituents responsible for bacterial vaginosis. When the data were stratified by these potential confounders, the levels of all 3 proinflammatory endocervical cytokines were significantly higher in pregnant women than in nonpregnant women. CONCLUSIONS The proinflammatory cytokine milieu in the cervix is enhanced in pregnant women with bacterial vaginosis, compared with that in nonpregnant women. The notion of pregnancy as an immune-compromised state may be anatomically compartment specific.