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BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Dengue virus serotypes 1 to 4 (DENV1–4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence after the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme-linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Unexpectedly, we found that overall DENV iELISA titers stabilized by 8 months after primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies after ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer set point, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

BACKGROUND: Zika virus (ZIKV) emerged in northeast Brazil in 2015 and spread rapidly across the Americas, in populations that have been largely exposed to dengue virus (DENV). The impact of prior DENV infection on ZIKV infection outcome remains unclear. To study this potential impact, we analyzed the large 2016 Zika epidemic in Managua, Nicaragua, in a pediatric cohort with well-characterized DENV infection histories. METHODS AND FINDINGS: Symptomatic ZIKV infections (Zika cases) were identified by real-time reverse transcription PCR and serology in a community-based cohort study that follows approximately 3,700 children aged 2-14 years old. Annual blood samples were used to identify clinically inapparent ZIKV infections using a novel, well-characterized serological assay. Multivariable Poisson regression was used to examine the relation between prior DENV infection and incidence of symptomatic and inapparent ZIKV infection. The generalized-growth method was used to estimate the effective reproduction number. From January 1, 2016, to February 28, 2017, 560 symptomatic ZIKV infections and 1,356 total ZIKV infections (symptomatic and inapparent) were identified, for an overall incidence of 14.0 symptomatic infections (95% CI: 12.9, 15.2) and 36.5 total infections (95% CI: 34.7, 38.6) per 100 person-years. Effective reproduction number estimates ranged from 3.3 to 3.4, depending on the ascending wave period. Incidence of symptomatic and total ZIKV infections was higher in females and older children. Analysis of the effect of prior DENV infection was performed on 3,027 participants with documented DENV infection histories, of which 743 (24.5%) had experienced at least 1 prior DENV infection during cohort follow-up. Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1-2 years before ZIKV infection). Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections. Our findings are limited to a pediatric population and constrained by the epidemiology of the site. CONCLUSIONS: These findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.

This article aims to reflect on the teaching practices in universities of Catholic inspiration. Our study argues that the university should be a place for cultivating wisdom, not merely for transmitting specialized knowledge. This thesis is grounded in the idea that universities are engaged in a systematic pursuit of truth in its various forms. While primarily theoretical, our research is also informed by recent studies on the development of critical thinking within the academic environment. The connection between truth and wisdom suggests that ongoing engagement with reality deepens our understanding of the relationships among things, enabling us to distinguish between means and ends, and what is appropriate from what is not. Wisdom involves understanding the meaning of things and placing them in their proper context—an outlook that universities should foster in students. Although phronesis, the practical dimension of wisdom, cannot be directly taught, a high-quality university education can bridge the gap between theory and daily life. This connection is reflected in the promotion of a sound critical mindset, where the professor's primary goal is to stimulate active learning. This can be achieved through diverse methods and creative teaching approaches. In a Catholic university, the search for truth is intrinsically linked to intellectual development and community service, guiding individuals closer to God, the source of all wisdom. [ABSTRACT FROM AUTHOR]

Vanadium is a strategic metal that has many important industrial applications and is generated by the use of burning fossil fuels, which inevitably leads to their release into the environment, mainly in the form of oxides. The wastes generated by their use represent a major health hazard. Furthermore, it has attracted attention because several genotoxicity studies have shown that some vanadium compounds can affect DNA; among the most studied compounds is vanadium pentoxide, but studies in vivo with oxidation states IV and III are scarce and controversial. In this study, the genotoxic and cytotoxic potential of vanadium oxides was investigated in mouse bone marrow cells using structural chromosomal aberration (SCA) and mitotic index (MI) test systems. Three groups were administered vanadium(IV) tetraoxide (V2O4) intraperitoneally at 4.7, 9.4 or 18.8 mg/kg, and three groups were administered vanadium(III) trioxide (V2O3) at 4.22, 8.46 or 16.93 mg/kg body weight. The control group was treated with sterile water, and the positive control group was treated with cadmium(II) chloride (CdCl2). After 24 h, all doses of vanadium compounds increased the percentage of cells with SCA and decreased the MI. Our results demonstrated that under the present experimental conditions and doses, treatment with V2O4 and V2O3 induces chromosomal aberrations and alters cell division in the bone marrow of mice. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the most prevalent human vector-borne viral disease. The force of infection (FoI), the rate at which susceptible individuals are infected in a population, is an important metric for infectious disease modeling. Understanding how and why the FoI of DENV changes over time is critical for developing immunization and vector control policies. We used age-stratified seroprevalence data from 12 years of the Pediatric Dengue Cohort Study in Nicaragua to estimate the annual FoI of DENV from 1994 to 2015. Seroprevalence data revealed a change in the rate at which children acquire DENV-specific immunity: in 2004, 50% of children age >4 years were seropositive, but by 2015, 50% seropositivity was reached only by age 11 years. We estimated a spike in the FoI in 1997-1998 and 1998-1999 and a gradual decline thereafter, and children age

Zika virus (ZIKV) is a mosquito-borne flavivirus that is responsible for recent explosive epidemics in the Americas. Notably, ZIKV infection during pregnancy has been found to cause congenital birth defects, including microcephaly, and ZIKV has been associated with Guillain-Barré syndrome in adults. Diagnosis and surveillance of Zika in the Americas have been challenging due to similar clinical manifestations and extensive antibody cross-reactivity with endemic flaviviral diseases, such as dengue. We evaluated four serological and two reverse transcription-PCR (RT-PCR) methods in acute-phase (mean day, 1.8), early-convalescent-phase (mean day, 16.7), and late-convalescent-phase (mean, ~7 months) samples from the same individuals in a long-term pediatric cohort study in Nicaragua. Well-characterized samples from 301 cases of Zika, dengue, or non-Zika, nondengue febrile illnesses were tested. Compared to a composite reference, an in-house IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the NIAID-Biodefense and Emerging Infections (BEI) MAC-ELISA measuring IgM yielded sensitivities of 94.5% and 70.1% and specificities of 85.6% and 82.8%, respectively. The NS1 blockade-of-binding ELISA measuring anti-ZIKV NS1 antibody levels yielded sensitivities of 85.0% and 96.5% and specificities of 91.4% and 92.6% at early and late convalescence, respectively. An inhibition ELISA detecting total anti-ZIKV antibodies had sensitivity and specificity values of 68.3% and 58.3% for diagnosis and 94.0% and 98.6% for measuring annual infection incidence. Finally, the ZCD and Trioplex real-time RT-PCR assays detecting Zika, chikungunya, and dengue viruses both yielded a sensitivity of 96.1% and specificity of 100%. Together, these assays resolve the urgent need for diagnostic and surveillance tools for countries affected by Zika virus infections.