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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. The prevalence of metabolic syndrome (MetS) within individual cohorts varies with the definition used. The aim of this study was to compare the prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri Lankan population and to investigate the characteristics of discrepant cases. Methods. 2985 individuals, aged 35–65 years, were recruited to the study. Anthropometric and blood pressure measurements and laboratory investigations were carried out following standard protocols. Results. Age and sex-adjusted prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions, respectively. IDF criteria failed to identify 21% of men and 7% of women identified by the revised NCEP criteria. The discrepant group had more adverse metabolic profiles despite having a lower waist circumference than those diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan cohort regardless of the definition used. The revised NCEP definition was more appropriate in identifying the metabolically abnormal but nonobese individuals, especially among the males predisposed to type 2 diabetes or cardiovascular disease. Further research is needed to determine the suitability of the currently accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults.

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.

Objectives Quantifying the risk of cardiovascular disease (CVD) in a community is important in planning preventive strategies, but such data are limited from developing countries, especially South Asia. We aimed to estimate the risks of coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan community.Methods A community survey was conducted in an urban health administrative area among individuals aged 35-64 years, selected by stratified random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were estimated using three risk prediction tools: National Cholesterol Education Program -Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk Evaluation (SCORE), and World Health Organisation/ International Society of Hypertension (WHO/ISH) charts.Results Among study participants (n=2985), 54.5% were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk) criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5-13.1) respectively were classified as at 'high risk'. The proportion of high risk participants increased with age. 'High risk' was commoner among males (30.3% vs 20.6%, p<0.001) according to NCEP-ATP III criteria, but among females (9.7% vs. 6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference was noted in SCORE risk categories.Conclusions A large proportion of individuals in this community are at risk of developing cardiovascular diseases, especially in older age groups. Risk estimates varied with the different prediction tools, and were comparatively higher with NCEP-ATP III charts.

Epidemiologic studies from South Asian countries have reported vitamin D deficiency among all age groups. However, there is very little information on vitamin D levels, especially in the vulnerable populations (pregnant/breast feeding mother and infants) in Sri Lanka. More data on vitamin D status of such populations will be important for policy decisions to be made at a national level. Similarly, it will be valuable for healthcare programs in other countries (e.g., United States, Australia, Europe, and Canada) as Sri Lankans are a fast-growing migrant population to those countries. The purpose of this study was to investigate maternal vitamin D status and its effects on infants in a state sector tertiary care centre in Sri Lanka. This prospective cohort study was conducted on 140 healthy pregnant mothers in the third trimester (mean gestational age 39±1 weeks). Blood was collected for 25(OH)D and parathyroid hormone (PTH). Sun exposure and feeding patterns of the infants were recorded based on maternal reporting. Mean age of the infants at follow-up visit was 36±7 days. Vitamin D (25 (OH)D) deficiency (<25 nmol/L) was observed in 12% pregnant mothers, 5% lactating mothers, and 63% infants. Insufficiency (<50 nmol/L) was found in an additional 51% and 43% in pregnant and lactating mothers and 25% of infants. Mean 25(OH)D was higher in pregnant (46.4±17.5 nmol/L) and lactating (51.9±17.0 nmol/L) mothers than infants (28.1±13.7 nmol/L). Maternal vitamin D level during pregnancy was a significant risk factor (OR: 6.00, 95%CI: 1.522-23.655) for infant deficiency and insufficiency. Sun exposure of infants showed a significant positive correlation with vitamin D level (OR: 3.23, 95%CI: 1.19-8.68). In conclusion, the presence of Vitamin D deficiency/insufficiency is higher in infants compared to pregnant/lactating mothers. Low maternal 25(OH)D during pregnancy was a risk factor for deficiency in infants. Although majority of lactating mothers had sufficient vitamin D, most of their exclusively breastfed offspring were deficient.

Background We evaluated the clinical outcomes, functional burden, and complications one month after COVID-19 infection in a prospective United States Military Health System (MHS) cohort of active duty, retiree, and dependent populations using serial patient-reported outcome surveys and electronic medical record (EMR) review. Methods MHS beneficiaries presenting at nine sites across the United States with a positive SARS-CoV-2 test, a COVID-19 like illness, or a high-risk SARS-CoV-2 exposure were eligible for enrollment. Medical history and clinical outcomes were collected through structured interviews and ICD-based EMR review. Risk factors associated with hospitalization were determined by multivariate logistic regression. Results A total of 1,202 participants were enrolled. There were 1,070 laboratory confirmed SARS-CoV-2 cases and 132 SARS-CoV-2 negative participants. In the first month post-symptom onset among the SARS-CoV-2 positive cases, there were 214 hospitalizations, 79% requiring oxygen, 22 ICU admissions, and 9 deaths. Risk factors for COVID-19 associated hospitalization included race (increased for Asian, Black, and Hispanic compared to non-Hispanic White), age (age 45-64 and 65+ compared to &lt;45), and obesity (BMI&gt;=30 compared to BMI&lt;30). Over 2% of survey respondents reported the need for supplemental oxygen and 31% had not returned to normal daily activities at one-month post-symptom onset. Conclusions Older age, reporting Asian, Black or Hispanic race/ethnicity, and obesity are associated with SARS-CoV-2 hospitalization. A proportion of acute SARS-CoV-2 infections require long-term oxygen therapy; the impact of SARS-CoV-2 infection on short-term functional status was substantial. A significant number of MHS beneficiaries had not yet returned to normal activities by one month.