The Zika Virus Infection in Pregnancy: Review and Implications for Research and Care of Women and Infants in Affected Areas.

The world has encountered a new and serious epidemic which has disproportionately affected fetuses and infants. What makes the Zika virus (ZIKV) epidemic such a threat in our times, is that a whole generation can be affected by birth defects caused by a seemingly innocuous maternal infection, which in most cases go unnoticed and undiagnosed. Spreading to over 80 countries and affecting millions, it is associated with severe birth defects known as congenital Zika syndrome (CZS), which include fetal brain development abnormalities (microcephaly and brain calcifications), retinal abnormalities, and contractures and hypertonia of the extremities. Testing strategies are challenging because of the lack of symptoms and cross reactivity with other viral infections. Obstetrical complications include fetal loss and the need for an emergency cesarean delivery. The rate of CZS has been described as ranging from 5 to 6% among cohorts in the US, reaching 11% for 1st trimester exposure. Prolonged viremia during pregnancy has been documented in a few cases, reaching 89 days after the onset of symptoms in one case and 109 days after such onset in another. If the ZIKV can infect, multiply in, and persist in diverse placental cells, then movement across the placenta, the fetal brain, and the maternal peripheral blood is possible. There is a sense of urgency, and we need safe and effective vaccines and treatments, particularly for pregnant women. If we do not expand testing and develop methods for early diagnosis and treatment, thousands of infants will be exposed to a neurotropic virus that causes severe birth defects and that could also affect the lives of those who form the next generation.

HIV seroconversion during pregnancy and the need for pre-exposure prophylaxis (PrEP).

The reduction in the mother-to-infant transmission of HIV has been among the early successes of care and treatment of women living with HIV. Prenatal HIV counseling and testing, the availability of diverse antiretroviral therapies, elective cesarean section, and the use of formula milk have significantly reduced the mother-to-infant transmission in the USA and Europe. We are presenting two cases of seroconversion during pregnancy, identified during labor and delivery, of women who received risk reduction counseling and serial HIV testing during pregnancy. Because there are no guidelines for (or easy access to) the use of pre-exposure prophylaxis (PrEP) in pregnancy, they were offered other strategies for prevention including risk reduction counseling, condoms, and serial HIV testing. These cases support the use of PrEP during pregnancy. Both infants were negative and the women are currently receiving long-term highly active antiretroviral therapy. One of them recently delivered another infant. After these two women seroconverted, we decided to offer PrEP to all pregnant women presenting for care who report having an HIV positive partner. During the period 2012-2014, we treated ten HIV negative pregnant women who were partners of HIV positive men. Since 2015, we have seen 20 pregnant women in HIV discordant relationships. Of those, seven received PrEP. No seroconversions have been observed among the pregnant women on PrEP. Although small numbers, seroconversion during pregnancy was observed in two of 13 (15%) of the pregnant women in HIV-discordant relationships seen in our clinic, excluding those treated with PrEP. Given the safety data and experience with tenofovir and emtricitabine among pregnant women living with HIV, we believe PrEP should be offered in pregnancy and that guidelines should reflect this option as an additional strategy to reduce risks during pregnancy and to further reduce infant HIV transmission risk.

Biomedical HIV prevention strategies: state of the art and implications for public health policy in the Caribbean.

Recent advances in the field of biomedical prevention have induced optimism among both the scientific community and the public in general. The discussion of the research evidence is complemented with a discussion of the implications of this evidence for the Caribbean, highlighting the issues and controversies that should be considered in order to encourage and advance the responsible consideration of biomedical strategies. Traditionally, HIV prevention strategies have been characterized as predominantly behavior, social or biomedical. In practice, however, some strategies defy classification: even when they rely on technological or pharmaceutical elements, they have to be adopted by a society and the individuals within it. Moreover, whatever the strategy used, it will have to be distributed, implemented and made available through health care systems or other means. And its cost will be absorbed by specific funders or by society in general. Given the current historical context of the HIV/AIDS epidemic and the array of strategies required to control it, these distinctions (biomedical vs. behavior) can hinder the collaborations required to provide the needed combinations of strategies. The efficacy of the diverse strategies range from: 99% for programs to prevent MTCT, 63% for pre-exposure prophylaxis (PrEP), 96% for treatment as prevention, 39% for vaginal microbicides (54% with good adherence), post exposure prophylaxis (PEP), 31% for a vaccine and 53-60% for medical voluntary adult circumcision. To curtail and eliminate the HIV/AIDS epidemic in the future, expansion and scaled-up implementation of combinations of such strategies will be needed.

Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis.

BACKGROUND: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. RESULTS: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. CONCLUSIONS: We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.