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BackgroundSeasonal influenza vaccination uptake among young children in Thailand is low despite national recommendation for vaccination. We implemented a knowledge, attitude/perception, and practice survey to understand determinants of influenza vaccination in children aged six months to two years.MethodsUsing a cross-sectional design, we interviewed caregivers of 700 children in seven hospitals using a structured questionnaire to collect information on caregivers' and children's demographic characteristics, and caregivers' knowledge of influenza illness and national vaccine recommendation, attitude/perception toward influenza vaccine, and information sources. We verified children's influenza vaccination status against medical records (vaccinated vs. unvaccinated). Logistic regression was used to examine factors independently associated with children receiving influenza vaccination in the 2018 season using the dataset restricted to only children's parents. Variables associated with vaccination at p-value ≤0.20 were included in subsequent multivariable logistic models. Significant independent determinants of children's influenza vaccination and collinearity of covariates were assessed. The final model was constructed using a stepwise backward elimination approach with variables significant at p-value ResultsDuring August 2018-February 2019, 700 children's caregivers completed the questionnaire; 61 (9%) were caregivers of vaccinated children. Caregivers of the vaccinated children were statistically more likely to have higher education (61% vs. 38%; p-valueConclusionThe majority of caregivers of children in this study had knowledge of influenza illness and influenza vaccine. Caregivers reported various sources of information regarding influenza illness and the vaccine, but healthcare providers remained the most trusted source. Children's history of influenza vaccination in prior season(s) was the strongest determinant of children being vaccinated for influenza in the current season.

Thailand recommends influenza vaccination for children aged 6 months to

Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand.A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups.Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained).The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.

The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions.Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis.The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.

While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei "aerosols" in transmission is controversial.In Hong Kong and Bangkok, in 2008-11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7-10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%-72% risk of fever plus cough if infected via aerosol route, and a 23%-31% risk of fever plus cough if infected via the other two modes of transmission.Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.

Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure.This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT.158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB.Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.

Background: Seasonal influenza vaccination uptake among young children in Thailand is low despite national recommendation for vaccination. We implemented a knowledge, attitude/perception, and practice survey to understand determinants of influenza vaccination in children aged six months to two years., Methods: Using a cross-sectional design, we interviewed caregivers of 700 children in seven hospitals using a structured questionnaire to collect information on caregivers' and children's demographic characteristics, and caregivers' knowledge of influenza illness and national vaccine recommendation, attitude/perception toward influenza vaccine, and information sources. We verified children's influenza vaccination status against medical records (vaccinated vs. unvaccinated). Logistic regression was used to examine factors independently associated with children receiving influenza vaccination in the 2018 season using the dataset restricted to only children's parents. Variables associated with vaccination at p-value ≤0.20 were included in subsequent multivariable logistic models. Significant independent determinants of children's influenza vaccination and collinearity of covariates were assessed. The final model was constructed using a stepwise backward elimination approach with variables significant at p-value <0.05 retained in the model., Results: During August 2018-February 2019, 700 children's caregivers completed the questionnaire; 61 (9%) were caregivers of vaccinated children. Caregivers of the vaccinated children were statistically more likely to have higher education (61% vs. 38%; p-value<0.01) and to know of influenza illness (93% vs. 76%; p-value = 0.03) than those of the unvaccinated group. Factors associated with children receiving influenza vaccination were identifying healthcare providers as a primary source of information about influenza illness for parents (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.3-6.0), parents' strongly agreeing with the national recommendation for influenza vaccination in young children (aOR, 2.9; 95% CI, 1.5-5.9), using health insurance provided by the government or parent's employer for children's doctor visits (aOR, 2.6; 95% CI, 1.1-6.6), and the children's history of receiving influenza vaccination in the 2017 season or earlier (aOR, 3.2; 95% CI, 1.4-7.8)., Conclusion: The majority of caregivers of children in this study had knowledge of influenza illness and influenza vaccine. Caregivers reported various sources of information regarding influenza illness and the vaccine, but healthcare providers remained the most trusted source. Children's history of influenza vaccination in prior season(s) was the strongest determinant of children being vaccinated for influenza in the current season., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Thailand recommends influenza vaccination for children aged 6 months to <36 months, but investment in vaccine purchase is limited. To inform policy decision with respect to influenza disease burden and associated cost in young children and to support the continued inclusion of children as the recommended group for influenza vaccination, we conducted a prospective cohort study of children in Bangkok hospital to estimate and compare influenza incidence and cost between healthy and high-risk children., Methods: Caregivers of healthy children and children with medical conditions ('high-risk') aged <36 months were called weekly for two years to identify acute respiratory illness (ARI) episodes and collect illness-associated costs. Children with ARI were tested for influenza viruses by polymerase chain reaction. Illnesses were categorized as mild or severe depending on whether children were hospitalized. Population-averaged Poisson models were used to compare influenza incidence by risk group. Quantile regression was used to examine differences in the median illness expenses., Results: During August 2011-September 2015, 659 healthy and 490 high-risk children were enrolled; median age was 10 months. Incidence of mild influenza-associated ARI was higher among healthy than high-risk children (incidence rate ratio [IRR]: 1.67; 95% confidence interval [CI]: 1.13-2.48). Incidence of severe influenza-associated ARI did not differ (IRR: 0.40; 95% CI: 0.11-1.38). The median cost per mild influenza-associated ARI episode was $22 among healthy and $25 among high-risk children (3-4% of monthly household income; difference in medians: -$1; 95% CI for difference in medians: -$9 to $6). The median cost per severe influenza-associated ARI episode was $232 among healthy and $318 among high-risk children (26-40% and 36-54% of monthly household income, respectively; difference in medians: 110; 95% CI for difference in medians: -$352 to $571)., Conclusions: Compared to high-risk children, healthy children had higher incidence of mild influenza-associated ARI but not severe influenza-associated ARI. Costs of severe influenza-associated ARI were substantial. These findings support the benefit of annual influenza vaccination in reducing the burden of influenza and associated cost in young children., Competing Interests: The authors have declared that no competing interests exist.

Background: Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand., Methods: A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups., Results: Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained)., Conclusion: The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.

Background: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions., Methodology/principal Findings: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis., Conclusion/significances: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.

Introduction: While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei "aerosols" in transmission is controversial., Methods and Findings: In Hong Kong and Bangkok, in 2008-11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7-10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%-72% risk of fever plus cough if infected via aerosol route, and a 23%-31% risk of fever plus cough if infected via the other two modes of transmission., Conclusions: Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.

Background: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure., Methods: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT., Results: 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB., Conclusions: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.