Pregnancy Outcomes among Women Receiving rVSVΔ-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola.

Little information exists regarding Ebola vaccine rVSVΔG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Recent trends in hepatic diseases during pregnancy in the United States, 2002-2010.

OBJECTIVE: While pregnancy-related severe liver disorders are rare, when they occur morbidity and mortality rates are increased for mothers and infants. The objective of this study was to examine the prevalence and trends of hepatic diseases during pregnancy hospitalizations from 2002 through 2010 in the United States. STUDY DESIGN: Hospital discharge data were obtained from the Nationwide Inpatient Sample, the largest all-payer hospital inpatient care database in the United States that provides nationally representative estimates. Pregnancy hospitalizations with the following diagnoses were identified: hepatitis B, hepatitis C, gallbladder disease/cholelithiasis, liver disorders of pregnancy, chronic/alcohol-related liver disease, biliary tract disease, and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Age, insurance status, hospital location, and hospital region were compared among women with and without hepatic diseases using a χ(2) test. Trends in rates of pregnancy hospitalizations and mean charges were analyzed using multivariable logistic and linear regression, respectively. RESULTS: From 2002 through 2010 there were an estimated 41,479,358 pregnancy hospitalizations in the United States. Gallbladder disease and liver disorders of pregnancy were the most common hepatic diseases (rates = 7.18 and 4.65/1000 pregnancy hospitalizations, respectively). Adjusted rates and mean charges significantly increased for all hepatic diseases during pregnancy over the study period. All hepatic diseases were associated with significantly higher charges compared to all pregnancy hospitalizations. HELLP syndrome was associated with the highest mean charges. CONCLUSION: This large study among a representative sample of the US population provides valuable information that can aid policy planning and management of these hepatic diseases during pregnancy in the United States.

Autoimmune haemolytic anaemia associated with Epstein Barr virus infection as a severe late complication after kidney transplantation and successful treatment with rituximab: case report.

BACKGROUND: Autoimmune haemolytic anaemia (AIHA) is a rare complication following kidney transplantation and usually occurs early in its course. It is characterised by autoantibodies or alloantibodies directed against red blood cells (RBCs). CASE PRESENTATION: We describe a 44 year old woman who presented 5 years after kidney transplantation with profound transfusion dependent warm AIHA. Investigations confirmed an IgG autoantibody against RBCs and high titre Epstein-Barr virus (EBV) viraemia. The patient was at higher risk for EBV disease being seronegative at the time of transplantation but had detectable EBV capsid IgG antibody at the time of presentation. The haemolysis was refractory to high dose steroid and intravenous immunoglobulin. There was a rapid and complete resolution of both the anaemia and the viraemia following rituximab therapy, with no adverse events. Twenty-six units of blood were required during the course of treatment. CONCLUSIONS: To our knowledge this is the first reported case of EBV associated AIHA in a renal transplant recipient. It highlights a rare pathology associated with post-transplant EBV infection, of broad interest to transplant physicians, haematologists, and microbiologists, and the effective novel use of monoclonal anti-CD20 therapy.

Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.

Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol's teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4-9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11-20, PD 21-30, or PD 11-30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21-30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11-20 or PD 11-30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline's therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.

Soil resilience and recovery: rapid community responses to management changes.

BACKGROUND AND AIMS: Soil degradation is a major global problem; to investigate the potential for recovery of soil biota and associated key functions, soils were monitored during the early years of conversion between permanent grassland, arable cropping and bare fallow (maintained by regular tilling). Distinct differences in soil properties had become apparent 50 years after a previous conversion. METHODS: Subplots on previously permanent grassland, arable and bare fallow soil were converted to the two alternatives, generating 9 treatments. Soil properties (soil organic carbon, mesofauna, microbial community structure and activity) were measured. RESULTS: After 2 years, mesofauna and microbial abundance increased where plants were grown on previously bare fallow soils and declined where grassland was converted to bare fallow treatment. Overall prokaryote community composition remained more similar to the previous treatments of the converted plots than to the new treatments but there were significant changes in the relative abundance of some groups and functional genes. Four years after conversion, SOC in arable and bare fallow soils converted to grassland had increased significantly. CONCLUSIONS: Conversion to permanent grassland effectively replenished C in previously degraded soil; the soil microbiome showed significant conversion-related changes; plant-driven recovery was quicker than C loss in the absence of plants.

Contraception for individuals with sickle cell disease: a systematic review of the literature.

BACKGROUND: Women with sickle cell disease have an increased risk of pregnancy-related complications and need safe, effective contraceptive methods to prevent unintended pregnancy. STUDY DESIGN: We conducted a systematic review to examine the safety of hormonal and intrauterine contraceptive use among women with sickle cell disease. RESULTS: Eight articles met the inclusion criteria. The evidence was of fair to poor quality and suggested that progestin-only and combined hormonal contraception had no effect on frequency of sickle crises or other adverse events and no effect on hematologic parameters associated with sickle crises. No studies examined the risk of thromboembolism in combined hormonal contraceptive users with sickle cell disease. There was insufficient evidence to comment on the safety of intrauterine contraception. CONCLUSION: While data are limited, there is no evidence to suggest that hormonal contraceptive use among women with sickle cell disease is associated with an increased risk of clinical complications.

Prevention of mother-to-child transmission of HIV-1: the role of cesarean delivery.

The risk of mother-to-child transmission (MTCT) of HIV can be reduced through cesarean delivery prior to the onset of labor and prior to rupture of the membranes (elective cesarean delivery [ECD]). As a result of this evidence, the American College of Obstetricians and Gynecologists and the Department of Health and Human Services Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission developed guidelines recommending ECD for HIV-infected women with plasma viral loads of more than 1000 copies/mL. Since the release of the recommendations, an increase in ECD has been seen among HIV-infected women in the United States. This article discusses the evidence on efficacy of ECD, current recommendations in the United States, and risks and morbidity related to ECD. Although the benefit of ECD in preventing MTCT of HIV is substantial, some questions remain. Specifically, the benefit of ECD for women with very low viral loads or for women using combination antiretroviral regimens is unclear, as is the timeframe after onset of labor or rupture of membranes within which ECD will still confer preventive benefits.