Serological Evidence of Japanese Encephalitis Virus Circulation in Asian Children From Dengue-Endemic Countries.

Background: Japanese encephalitis virus (JEV) is a zoonotic, mosquito-borne flavivirus, distributed across Asia. Infections are mostly mild or asymptomatic, but symptoms include neurological disorders, sequelae, and fatalities. Data to inform control strategies are limited due to incomplete case reporting. Methods: We used JEV serological data from a multicountry Asian dengue vaccine study in children aged 2-14 years to describe JEV endemicity, measuring antibodies by plaque reduction neutralization test (PRNT50). Results: A total 1479 unvaccinated subjects were included. A minimal estimate of pediatric JEV seroprevalence in dengue-naive individuals was 8.1% in Indonesia, 5.8% in Malaysia, 10.8% in the Philippines, and 30.7% in Vietnam, translating to annual infection risks varying from 0.8% (in Malaysia) to 5.2% (in Vietnam). JEV seroprevalence and annual infection estimates were much higher in children with history of dengue infection, indicating cross-neutralization within the JEV PRNT50 assay. Conclusions: These data confirm JEV transmission across predominantly urban areas and support a greater emphasis on JEV case finding, diagnosis, and prevention.

Health-related quality of life, temperament, and eating behavior among formula-fed infants in the Philippines: a pilot study.

BACKGROUND: The rising prevalence of childhood obesity in Asia has led to interest in potential risk factors such as infant health-related quality of life (HRQoL), temperament and eating behaviors. This pilot study evaluated the utility of administering parent-reported outcome measures (PROMs) to explore these factors in Filipino infants and examined the relationships between these factors and infant sex, formula intake and weight, over time. METHODS: Forty healthy, 4-week-old, formula-fed infants (n = 20 males) were enrolled in this 6-week, prospective, uncontrolled study during which infants were exclusively fed a standard term infant formula enriched with alpha-lactalbumin. On Day-1 and 42, anthropometrics were measured and mothers completed a 97-item measure of HRQoL [Infant Toddler Quality of Life Questionnaire (ITQOL)] covering 6 infant-focused and 3 parent-focused concepts and a 24-item measure of infant temperament [Infant Characteristics Questionnaire (ICQ)]. At Day-42, mothers also completed an 18-item measure of infant appetite [Baby Eating Behaviour Questionnaire (BEBQ)]. A 3-day formula intake diary was completed before Day-42. Nonparametric statistics were used to evaluate correlations among outcomes and compare outcomes by visit and sex. RESULTS: Thirty-nine infants completed the study; similar results were observed in males and females. Completion of PROMs was 100% with no missing responses, but Cronbach's α was low for many concept scales scores. ITQOL scores [range 0 (worst)-100 (best)] were generally high (median ≥ 80) except for Day-1 and Day-42 Temperament and Mood and Day-1 General Health Perceptions scores. ITQOL but not ICQ temperament scores improved significantly between Day-1 and Day-42 (P < 0.01). Mean ± standard deviation BEBQ scores (range 1-5) were high for Enjoyment of Food (4.59 ± 0.60) and Food Responsiveness (3.53 ± 0.81), and low for Satiety Responsiveness (2.50 ± 0.73) and Slowness in Eating (1.71 ± 0.60). Better HRQoL scores were significantly (P < 0.05) associated with high General Appetite scores (3 ITQOL concepts, r = 0.32 to 0.54), greater Enjoyment of Food (4 ITQOL concepts, r = 0.35 to 0.42) and low levels of Slowness in Eating (7 ITQOL concepts, r = - 0.32 to - 0.47). CONCLUSION: Findings demonstrated the utility of the ITQOL, ICQ and BEBQ for measuring HRQoL, temperament and eating behavior, and the need for further adaptations for use in Filipino infants. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02431377; Registered May 1, 2015.

Symptomatic Dengue in Children in 10 Asian and Latin American Countries.

BACKGROUND: The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic. METHODS: We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria. RESULTS: Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America. CONCLUSIONS: The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).

Effects of term infant formulas containing high sn-2 palmitate with and without oligofructose on stool composition, stool characteristics, and bifidogenicity.

OBJECTIVES: Levels of stool fatty acid soaps and beneficial bacteria differ between formula-fed and breast-fed infants; addition of specific formula ingredients may reduce these differences. This study evaluated the effects of a term infant formula containing high sn-2 palmitate term infant formula (sn-2) or an identical formula supplemented with oligofructose (OF) at 2 concentrations (sn-2+3 g/L OF, sn-2+5 g/L OF) on stool composition, stool characteristics, and fecal bifidobacteria. METHODS: Healthy, term formula-fed infants 7 to 14 days old (n = 300) were randomized in a double-blind manner to receive standard formula (control), sn-2, sn-2+3 g/L OF, or sn-2+5 g/L OF for 8 weeks. Human milk (HM)-fed infants (n = 75) were studied in parallel. Stool samples were collected from all subjects at week 8 for fatty acid soaps and mineral content, and from a subset at baseline and week 8 for bifidobacteria. Stool characteristics were assessed via 3-day diary. RESULTS: The sn-2 group had 46% less stool soap palmitate (P < 0.001) and softer stools than control (20% more mushy soft stools, P = 0.026; 50% fewer formed stools, P = 0.003). Addition of OF resulted in even fewer formed stools versus control (65% fewer for sn-2+3 g/L OF, 79% fewer for sn-2+5 g/L OF), with 5 g/L OF more closely resembling that of HM-fed infants. Both sn-2 (P < 0.05) and sn-2 with OF groups (P < 0.01) had significantly higher fecal bifidobacteria concentrations than control at week 8, not differing from HM-fed infants. CONCLUSIONS: High sn-2-palmitate formulas led to reduced stool soaps, softer stools, and increased bifidobacteria, whereas addition of OF further improved stool consistency. Those modifications brought outcomes in formula-fed infants closer to that in HM-fed infants.

Preparing for dengue vaccine introduction in ASEAN countries: recommendations from the first ADVA regional workshop.

The independent, scientific and educational The Association of South East Asian Nations (ASEAN) Member States Dengue Vaccination Advocacy Steering Committee (ADVASC) was established in 2011 to address the practical challenges faced by ASEAN countries as they prepare for the eventual introduction of a dengue vaccine. ADVASC convened a workshop in September 2012 that drew together public health representatives and dengue experts from seven ASEAN countries in order to make practical recommendations to improve current surveillance and diagnostics for dengue to enable countries to assess consistently, and accurately communicate, the impact of a dengue vaccine. The workshop compared surveillance and diagnostic capacity in these ASEAN countries and made recommendations to streamline and harmonize key elements of these systems. In particular, attendees recommended the need for reconciliation and harmonization of the different World Health Organization guidelines, in use in ASEAN countries for case definition and surveillance of dengue.

Single-dose, live-attenuated Japanese encephalitis vaccine in children aged 12-18 months: randomized, controlled phase 3 immunogenicity and safety trial.

This trial in 1200 JE-vaccination naïve children (age 12-18 mo) in Thailand and the Philippines aimed to demonstrate consistency of three successive industrial scale manufacturing lots of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and consistency between industrial scale manufacturing lots and a fourth, development lot. Children received JE-CV from one of three successive industrial scale lots produced in Thailand (n = 899), or from a fourth development lot produced in the USA (n = 199), or hepatitis A control vaccine (n = 102). Antibodies were assessed by 50% plaque reduction neutralization test (PRNT(50)) at screening and Day 28. Seroconversion rates (titer of < 10 at baseline and ≥ 10 on Day 28, or a four-fold rise from a baseline titer of ≥ 10) were determined per group. Lot-to-lot consistency of seroconversion rate and GMT was demonstrated between the 3 industrial scale lots, and between these lots and the US lot. Seroconversion rate on pooled data 28 d after JE-CV vaccination (Thai lots) was 95.0% [95% confidence interval (CI); 93.3-96.3]. The safety profile of JE-CV was favorable and comparable with hepatitis A vaccine. There were no serious adverse events related to vaccination. This study demonstrated the consistency of three successive industrial scale JE-CV vaccine lots, as well as consistency with a development lot. The study also demonstrated that a single dose of JE-CV is well tolerated and elicits a high protective immune response, seroconverting 95% of JE-naïve Asian children aged 12-18 mo.