The emerging zika virus epidemic in the Americas: Research priorities

On February 1, 2016, the World Health Organization declared a “public health emergency of international concern” regarding neurological disorders associated with the rapid emergence of Zika virus (ZIKV) in the Americas. Since being detected in Brazil in early 2015, ZIKV has spread extensively, with most countries in Latin America and the Caribbean now reporting local transmission of the virus. An association between congenital ZIKV infection and birth defects, most prominently microcephaly, has prompted intense concern among health officials and the public

17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study

Background Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. Objective Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. Study Design This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17-hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of ≥1 injection of the drug. Results Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17-hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received ≥1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. Conclusion Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17-hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth

Is there a silver lining to the Zika virus epidemic in the Americas?

It is hard to find anything positive to say about an epidemic of an emerging virus that infects pregnant women, targets developing fetuses’ neural progenitor cells, and disrupts the sequence of neural development to cause a devastating syndrome resulting in lifelong disabilities. Infants with microcephaly became the faces of the Zika virus epidemic in the Americas, which affected almost all countries in the western hemisphere in 2014–17. By the end of 2017, Zika virus has nearly disappeared from the Americas as quickly as it emerged. Now that the dust is settling, what have the scientific and public health communities learned? Is there a silver lining to Zika’s devastation

Misclassification in defining and diagnosing microcephaly

Background: Several health agencies define microcephaly for surveillance purposes using a single criterion, a percentile or Z-score cut-off for newborn head circumference. This definition, however, conflicts with the reported prevalence of microcephaly even in populations with endemic Zika virus. Objective: We explored possible reasons for this conflict, hypothesising that the definition of microcephaly used in some studies may be incompletely described, lacking the additional clinical criteria that clinicians use to make a formal diagnosis. We also explored the potential for misclassification that can result from differences in these definitions, especially when applying a percentile cut-off definition in the presence of the much lower observed prevalence estimates that we believe to be valid. Methods: We conducted simulations under a theoretical bimodal distribution of head circumference. For different definitions of microcephaly, we calculated the sensitivity and specificity using varying cut-offs of head circumference. We then calculated and plotted the positive predictive value for each of these definitions by prevalence of microcephaly. Results: Simple simulations suggest that if the true prevalence of microcephaly is approximately what is reported in peer-reviewed literature, then relying on cut-off-based definitions may lead to very poor positive predictive value under realistic conditions. Conclusions: While a simple head circumference criterion may be used in practice as a screening or surveillance tool, the definition lacks clarification as to what constitutes true pathological microcephaly and may lead to confusion about the true prevalence of microcephaly in Zika-endemic areas, as well as bias in aetiologic studies

Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia

Objectives.: HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia. Methods.: We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test®) and HPV typing using the Roche Linear Array® PCR assay. Results.: The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/μL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p = 0.02). Conclusions.: The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC

Neurodevelopmental Outcomes of Children following in Utero Exposure to Zika in Nicaragua

Background: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. Methods: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. Results: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P =. 01) and low-birthweight infants (<2500 g) (P =. 006) had lower composite ECL scores. Conclusions: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months

Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia

OBJECTIVE : To evaluate the safety of combination antiretroviral therapy (ART) in conception and pregnancy in different health systems. DESIGN : A pilot ART registry to measure the prevalence of birth defects and adverse pregnancy outcomes in South Africa and Zambia. METHODS : HIV-infected pregnant women on ART prior to conception were enrolled until delivery, and their infants were followed until 1 year old. RESULTS : Between October 2010 and April 2011, 600 women were enrolled. The median CD4þ cell count at study enrollment was lower in South Africa than Zambia (320 vs. 430 cells/ml; P<0.01). The most common antiretroviral drugs at the time of conception included stavudine, lamivudine, and nevirapine. There were 16 abortions (2.7%), 1 ectopic pregnancy (0.2%), 12 (2.0%) stillbirths, and 571 (95.2%) live infants. Deliveries were more often preterm (29.7 vs. 18.4%; P¼0.01) and the infants had lower birth weights (2900 vs. 2995 g; P¼0.11) in Zambia compared to South Africa. Thirty-six infants had birth defects: 13 major and 23 minor. There were more major anomalies detected in South Africa and more minor ones in Zambia. No neonatal deaths were attributed to congenital birth defects. CONCLUSIONS : An Africa-specific, multi-site antiretroviral drug safety registry for pregnant women is feasible. Different prevalence for preterm delivery, delivery mode, and birth defect types between women on preconception ART in South Africa and Zambia highlight the potential impact of health systems on pregnancy outcomes. As countries establish ART drug safety registries, documenting health facility limitations may be as essential as the specific ART details.President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of Cooperative Agreements U62/CCU123541, 3U2GGH000175–01W1, and 3U2GPS001421.http://www.lww.com/product/?0269-9370hb201

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters