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IMPORTANCECurrent guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika virus in utero.OBJECTIVE To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction-confirmed Zika virus infection during pregnancy.DESIGN, SETTING, AND PARTICIPANTS In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil.PARTICIPANTS Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus.MAIN OUTCOMES AND MEASURES Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection. RESULTSOf the 112 with polymerase chain reaction-confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio [OR], 19.1; 95% CI, 6.0-61.0), other central nervous system abnormalities (OR, 4.

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IMPORTANCE Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. OBJECTIVE To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. EXPOSURES Zika virus infection during pregnancy. MAIN OUTCOMES AND MEASURES Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). RESULTS Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (

Summary:We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 ؋ 10 7 CD3 ؉ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m 2 /4 days and melphalan 70 mg/m 2 /2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n ‫؍‬ 4), MDS (n ‫؍‬ 1), ALL (n ‫؍‬ 3), CML (n ‫؍‬ 3) and multiple myeloma (n ‫؍‬ 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n ‫؍‬ 3), acute GVHD (n ‫؍‬ 3), chronic GVHD (n ‫؍‬ 1) and disease relapse (n ‫؍‬ 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day ؉30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear. The therapeutic benefit of allogeneic BMT is in part related to an immunological graft-versus-leukemia (GVL) effect that frequently evolves in the context of graft-versus-host disease (GVHD). The ability of donor lymphocytes to induce remission in patients relapsing after allogeneic transplantation illustrates the potency of this effect.1 Establishing donor-recipient tolerance with less toxic regimens may provide the basis for further immunological manipulations in order to maximize the GVL effect. However, rapidly evolving diseases may not be amenable to this strategy, considering that the immune-mediated elimination of malignant cells may take weeks or months to occur. This fact suggests the need for strategies to reinforce the immune-mediated phenomena in the post-transplant period.Groups in Jerusalem and Houston pioneered the use of sub-lethal doses of fludarabine-based conditioning regimens. These regimens have been shown to be less toxic and to provide enough immunosuppression to prevent graft rejection and establish stable mixed or complete chimerism.2,3 The combination of melphalan and fludarabine has enabled allogeneic stem cell engraftment in the majority of patients treated, at least in the setting of HLA-identical transplantation. Patients with refractory relapses of advanced leukemias appear to benefit the least.

Key Points Question Are neuroimaging findings of infants exposed to Zika virus associated with infant clinical outcomes and gestational age of antenatal Zika virus infection? Findings In this cohort study of 110 infants with confirmed or suspected antenatal exposure to Zika virus evaluated at a referral center from 2015 to 2016, 96% of abnormal neuroimaging occurred among Zika virus–exposed infants with severe clinical findings at birth; however, 10% of infants without severe clinical manifestations also had neuroimaging abnormalities. In addition, an increased risk of abnormal imaging was associated with Zika virus exposure in the first trimester compared with later trimesters. Meaning Neuroimaging of infants exposed to Zika virus is an important part of evaluating infants with a history of Zika virus in utero exposure, particularly for those exposed in the first trimester.

Similar eye manifestations were identified regardless of laboratory confirmation. Well-appearing infants were also found to have eye abnormalities. Therefore, all infants born after ZIKV outbreaks should be universally screened for eye abnormalities.

The killing of antigen-bearing cells by clonal populations of cytotoxic T lymphocytes (CTLs) is thought to be a rapid phenomenon executed uniformly by individual CTLs. We combined bulk and single-CTL killing assays over a prolonged time period to provide the killing statistics of clonal human CTLs against an excess of target cells. Our data reveal efficiency in sustained killing at the population level, which relied on a highly heterogeneous multiple killing performance at the individual level. Although intraclonal functional heterogeneity was a stable trait in clonal populations, it was reset in the progeny of individual CTLs. In-depth mathematical analysis of individual CTL killing data revealed a substantial proportion of high-rate killer CTLs with burst killing activity. Importantly, such activity was delayed and required activation with strong antigenic stimulation. Our study implies that functional heterogeneity allows CTL populations to calibrate prolonged cytotoxic activity to the size of target cell populations.