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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: In advance of a large influenza vaccine effectiveness (VE) cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness., Method: We selected adults ≥65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Survey (VES); scores ≥3 indicated vulnerability. Questions about attitudes towards vaccination were based on the Health Belief Model. The distance between participants' households and the nearest vaccination clinic was calculated. Vaccination status was determined using national influenza vaccination registry. Prevalence ratios (PR) and 95% confidence intervals (CIs) were calculated using log-binomial multivariable models accounting for the sampling design., Result: We enrolled 581 participants, of whom 60% were female, median age was 72 years, 41% had at least one chronic underlying illness, 24% met the criteria for vulnerable, and 23% did not leave the house on a daily basis. Influenza vaccination rate was 34%. In multivariable models, no variable related to functional status was associated with vaccination. The strongest predictors of vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7-5.1 for participants in the closest quartile compared to the furthest), and high levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4-5.6) and cues to action (PR 2.7, 95% CI 1.5-5.1)., Conclusion: Distance to vaccination clinics should be considered in analyses of influenza VE studies in Thailand. Strategies that emphasize benefits of vaccination and encourage physicians to recommend annual influenza vaccination could improve influenza vaccine uptake among older Thai adults. Outreach to more distant and less mobile older adults may also be required to improve influenza vaccination coverage.

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: Physicians play a major role in influencing acceptance and uptake of vaccines. However, little is known about physicians' perspectives on influenza vaccination of pregnant women in Thailand, for whom vaccine coverage is estimated at <1%., Method: In 2013, a self-administered questionnaire on physicians' perceptions, attitudes and practices related to influenza vaccination for pregnant women was distributed to 1,134 hospitals with an antenatal care clinic (ANC) in Thailand. At each hospital, one physician working at the ANC completed the survey. Predictors of routine recommendation of influenza vaccine were analyzed utilizing log-binomial regression., Results: A total of 580 (51%) complete responses were received from physicians practicing at ANCs. A favorable attitude towards vaccination was expressed by 436 (75%) physicians, however only 142 (25%) reported routinely recommending influenza vaccine to pregnant women in their current practice. Physicians were more likely to recommend influenza vaccine routinely when they had more than three years of practice (prevalence ratio [PR] 1.9, 95% CI 1.2-2.3), had treated pregnant women for influenza (PR 1.8, 95% CI 1.3-2.7), perceived the influenza vaccine to be effective (moderate level: PR 1.6, 95% CI 1.1-2.4; high level: PR 1.9, 95% CI 1.3-2.9) and were aware of the Ministry of Public Health's (MOPH) recommendation of influenza vaccination in pregnancy (PR 1.3, 95% CI 1.1-1.7). Vaccine not being available, perception that policy was ambiguous and lack of awareness of MOPH recommendations were the most commonly cited barriers to routine recommendation of influenza vaccine., Conclusion: Despite a national policy to vaccinate pregnant women for influenza, only 25% of Thai physicians working in ANCs routinely recommend vaccination. Strategies are needed to increase vaccine availability and free vaccine services, address clinician concerns over vaccine effectiveness and expand healthcare provider awareness of MOPH recommendations., Competing Interests: The authors have declared that no competing interests exist.

Background: Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described., Methods: Data from 2008-2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI)., Results: Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18-24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%., Conclusions: An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala.

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003-2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003-2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5-14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003-2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions.

Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to respiratory infections.

Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden., Methods and Findings: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009-July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129-27,659 for children <5 years old (2.9-4.7 per 1,000 persons) and 6,882-7,836 for persons ≥5 years old (0.21-0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065-2,259 (0.5-1.0 per 1,000 persons) among children <5 years old and 779-2,252 cases (0.1-0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases., Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.

Background: A new influenza A (H1N1) virus was first found in April 2009 and proceeded to cause a global pandemic. We compare the epidemiology and clinical presentation of seasonal influenza A (H1N1 and H3N2) and 2009 pandemic influenza A (H1N1) (pH1N1) using a prospective surveillance system for acute respiratory disease in Guatemala., Methodology/findings: Patients admitted to two public hospitals in Guatemala in 2008-2009 who met a pneumonia case definition, and ambulatory patients with influenza-like illness (ILI) at 10 ambulatory clinics were invited to participate. Data were collected through patient interview, chart abstraction and standardized physical and radiological exams. Nasopharyngeal swabs were taken from all enrolled patients for laboratory diagnosis of influenza A virus infection with real-time reverse transcription polymerase chain reaction. We identified 1,744 eligible, hospitalized pneumonia patients, enrolled 1,666 (96%) and tested samples from 1,601 (96%); 138 (9%) had influenza A virus infection. Surveillance for ILI found 899 eligible patients, enrolled 801 (89%) and tested samples from 793 (99%); influenza A virus infection was identified in 246 (31%). The age distribution of hospitalized pneumonia patients was similar between seasonal H1N1 and pH1N1 (P = 0.21); the proportion of pneumonia patients <1 year old with seasonal H1N1 (39%) and pH1N1 (37%) were similar (P = 0.42). The clinical presentation of pH1N1 and seasonal influenza A was similar for both hospitalized pneumonia and ILI patients. Although signs of severity (admission to an intensive care unit, mechanical ventilation and death) were higher among cases of pH1N1 than seasonal H1N1, none of the differences was statistically significant., Conclusions/significance: Small sample sizes may limit the power of this study to find significant differences between seasonal influenza A and pH1N1. In Guatemala, influenza, whether seasonal or pH1N1, appears to cause severe disease mainly in infants; targeted vaccination of children should be considered.