Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods Healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and 77.1% (58.6%, 87.3%) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9%, 70.1%) against VCD and 86.0% (78.4%, 91.0%) against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while efficacy against hospitalized VCD was sustained at 70.8% (49.6%, 83.0%). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. Conclusions TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.
Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. Methods Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. Results Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. Conclusions TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further. Clinical Trials Registration. NCT02747927. Takeda’s tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4–16 year olds in dengue-endemic countries.
Prenatal intimate partner violence (P-IPV) can have significant adverse impacts on both mother and fetus. Existing P-IPV interventions focus on the safety of the mother and on reducing revictimization; yet expanding these to address the adverse impact on the fetus has considerable potential for preventing long-term negative developmental outcomes. In this review, we draw together evidence on major pathways linking exposure to P-IPV and child outcomes, arguing that these pathways represent potential targets to improve P-IPV intervention efforts. Using a narrative review of 112 articles, we discuss candidate pathways linking P-IPV to child outcomes, as well as their implications for intervention. Articles were identified via key word searches of social science and medical databases and by inspection of reference lists of the most relevant articles, including recent reviews and meta-analyses. Articles were included if they addressed issues relevant to understanding the effects of P-IPV on child outcomes via six core pathways: maternal stress and mental illness, maternal–fetal attachment, maternal substance use, maternal nutritional intake, maternal antenatal health-care utilization, and infection. We also included articles relevant for linking these pathways to P-IPV interventions. We conclude that developing comprehensive P-IPV interventions that target immediate risk to the mother as well as long-term child outcomes via the candidate mediating pathways identified have significant potential to help reduce the global burden of P-IPV.
IntroductionViolence against children is a health, human rights and social problem affecting approximately half of the world’s children. Its effects begin at prenatal stages with long-lasting impacts on later health and well-being. The Evidence for Better Lives Study (EBLS) aims to produce high-quality longitudinal data from cities in eight low- and middle-income countries—Ghana, Jamaica, Pakistan, the Philippines, Romania, South Africa, Sri Lanka and Vietnam—to support effective intervention to reduce violence against children. EBLS-Foundational Research (EBLS-FR) tests critical aspects of the planned EBLS, including participant recruitment and retention, data collection and analysis. Alongside epidemiological estimates of levels and predictors of exposure to violence and adversity during pregnancy, we plan to explore mechanisms that may link exposure to violence to mothers’ biological stress markers and subjective well-being.Methods and analysesEBLS-FR is a short longitudinal study with a sample of 1200 pregnant women. Data are collected during the last trimester of pregnancy and 2 to 6 months after birth. The questionnaire for participating women has been translated into nine languages. Measures obtained from mothers will include, among others, mental and physical health, attitudes to corporal punishment, adverse childhood experiences, prenatal intimate partner violence, substance use and social/community support. Hair and dry blood spot samples are collected from the pregnant women to measure stress markers. To explore research participation among fathers, EBLS-FR is recruiting 300 fathers in the Philippines and Sri Lanka.Ethics and disseminationThe study received ethical approvals at all recruiting sites and universities in the project. Results will be disseminated through journal publications, conferences and seminar presentations involving local communities, health services and other stakeholders. Findings from this work will help to adjust the subsequent stages of the EBLS project.
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