BACKGROUND: Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata. METHODS: We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection. We calculated the COI by household income strata and calculated the out-of-pocket (OOP) cost as a proportion of household income. RESULTS: We included 11 studies representing 11 LMICs. OOP expenses, as a proportion of annual household income, were highest among the lowest income quintile in 10 of 11 studies: in 4/4 studies among the general population, in 6/7 studies among children, 2/2 studies among older adults, and in the sole study for adults with chronic medical conditions. COI was generally higher for hospitalizations compared with outpatient illnesses; median OOP costs for hospitalizations exceeded 10% of annual household income among the general population and children in Kenya, as well as for older adults and adults with chronic medical conditions in China. CONCLUSIONS: The findings indicate that influenza and acute respiratory infections pose a considerable economic burden, particularly from hospitalizations, on the lowest income households in LMICs. Future evaluations could investigate specific drivers of COI in low-income household and identify interventions that may address these, including exploring household coping mechanisms. Cost-effectiveness analyses could incorporate health inequity analyses, in pursuit of health equity.

BACKGROUND: We examined the added value of serologic testing for estimating influenza virus infection incidence based on illness surveillance with molecular testing versus periodic serologic testing. METHODS: Pregnant persons unvaccinated against influenza at <28 weeks gestation were enrolled before the 2017 and 2018 influenza seasons in Peru and Thailand. Blood specimens were collected at enrollment and ≤14 days postpartum for testing by hemagglutination inhibition assay for antibodies against influenza reference viruses. Seroconversion was defined as a ≥4-fold rise in antibody titers from enrollment to postpartum with the second specimen's titer of ≥40. Throughout pregnancy, participants responded to twice weekly surveillance contacts asking about influenza vaccination and influenza-like symptoms (ILS). A mid-turbinate swab was collected with each ILS episode for influenza real-time reverse transcription PCR (rRT-PCR). RESULTS: Of 1,466 participants without evidence of influenza vaccination during pregnancy, 296 (20.2%) had evidence of influenza virus infections. Fifteen (5.1%) were detected by rRT-PCR only, 250 (84.4%) by serologic testing only, and 31 (10.5%) by both methods. CONCLUSIONS: Influenza virus infections during pregnancy occurred in 20% of cohort participants; >80% were not detected by a broad illness case definition coupled with rRT-PCR.

BACKGROUND: Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. METHODS: In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6-8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. RESULTS: Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25-35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (< 1%). Factors independently associated with cesarean delivery included age ≥ 25 years, pre-pregnancy obesity, new/worsen medical condition during pregnancy, fetal distress, abnormal labor, infant size for gestational age ≥ 50(th) percentiles, and self-pay for delivery fees. Women with existing blood conditions were less likely to have cesarean delivery. CONCLUSIONS: Almost one in two pregnancies among women in our cohorts resulted in cesarean deliveries. Compared to WHO guidelines, cesarean delivery rates were elevated in selected Robson groups indicating that tailored interventions to minimize non-clinically indicated cesarean delivery for specific groups of pregnancies may be warranted.

Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps.

INTRODUCTION: With the licensure of maternal RSV vaccines in Europe and USA, data are needed to better characterize the burden of respiratory syncytial virus (RSV)-associated acute respiratory infections (ARI) in pregnancy. This study aims to determine among pregnant individuals the proportion of ARI testing positive for RSV and RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review following PRISMA 2020 guidelines using five databases (Medline, Embase, Global Health, Web of Science and Global Index Medicus) and included additional unpublished data. Pregnant individuals with respiratory infections who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with respiratory infections that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% CI: 1.9; 54). The pooled incidence rate of RSV infection episodes among pregnant individuals was 26.0 (15.8; 36.2) per 1000 person-years. RSV hospitalization rates reported in two studies were 2.4 and 3.0 per 1000 person-years. Of five studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in odds of miscarriage, stillbirth, low birth weight, and small for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio 3.6 [1.3; 10.3]). CONCLUSION: Data on RSV-associated hospitalization incidence rates are limited but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions.

OBJECTIVES: Personal protective equipment (PPE) use is associated with reduced risk of SARS-CoV-2 infection among healthcare personnel (HCP). There are limited data on the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on the PPE use of HCP. We describe the changes in PPE use from just before the widespread of community outbreaks ('pre-pandemic') to intra-pandemic time points, and examine factors associated with not changing in PPE use behavior among HCP in four Thai hospitals. METHODS: We performed a retrospective cohort evaluation using two-time points: (i) February-March 2020 (pre-pandemic period); and (ii) January-March 2021 (intra-pandemic period). Self-reported frequency of appropriate PPE use was measured by a Likert scale. We used multivariable logistic regression to identify factors associated with no increase in self-reported PPE use. RESULTS: Of 343 HCP, the proportion of participants reporting 'always' using PPE rose from 66% during the pre-pandemic period to 80% during the pandemic. Factors associated with HCP who did not increase in PPE use included having high baseline reported PPE, being a non-registered HCP (e.g. nurse assistants, dental assistants, porters), being male, and having a low perceived risk of becoming infected with any respiratory virus while working in the hospital. CONCLUSION: PPE education, training, and risk communication content should target all cadres of HCP, regardless of registered/non-registered status, with a focus on behavior change for improved prevention and control of SARS-CoV-2 and other respiratory viruses in healthcare settings.

OBJECTIVES: We estimated influenza-like symptom (ILS) incidence among healthcare personnel (HCP) in four hospitals and the economic impact due to ILS in the Thai HCP population during July 2020-June 2021 (Thailand's expected 2020 influenza season), which also coincided with the novel coronavirus disease 2019 pandemic. METHODS: We followed HCP, in a prospective observational cohort, weekly for ≥1 of: muscle pain, cough, runny nose/nasal congestion, sore throat, or difficulty breathing. We fitted population-averaged Poisson regression models to identify factors associated with acquiring ILS and to calculate ILS incidence. We applied epidemiologic parameters to Thailand's HCP population (227 349 persons) to estimate economic impact. RESULTS: Of 2184 participants, adjusted all-cause ILS incidence was 6.1 episodes per 100 person-years (95% confidence interval 3.4-10.9). Among Thailand's HCP population, 13 909 ILS episodes were estimated to occur annually and would result in US$235 135 economic loss. Controlling for study site and calendar month, factors associated with acquiring ≥1 ILS versus no ILS included being female, having asthma, and using personal protective equipment 'frequently, but not always'. CONCLUSIONS: All-cause ILS resulted in considerable economic loss among Thai HCP workforce. These findings underscore the importance of public health interventions to reduce the risk of acquiring ILS.

Background: We examined the characteristics of healthcare providers’ (HCPs) encounters, and the frequency of worker absenteeism/presenteeism, among HCPs in inpatient wards at a tertiary-level public hospital in Bangkok, Thailand. The wards were stratified by risk of respiratory virus transmission: low-risk (Surgery, Rehabilitation, Orthopedic, and Obstetrics and Gynecology) and high-risk (Medicine, Pediatric, Emergency, and Ear, Nose, and Throat). Methods: Observers followed HCPs throughout one self-selected 8-hour work shift to record their interaction with others. An encounter was defined as a 2-way conversation with ≥3 words in the physical presence of ≥1 person at <3 feet distance; or a physical skin-to-skin touch. We administered structured questionnaires to document demographics, health and work history, past practice while ill, and recent and current acute muscle pain and/or respiratory symptoms. We collected data from time and attendance records of participants reporting illness within the past seven days. Results: From July to August 2019, 240 HCPs were enrolled and observed during 395 work shifts; 15,878 total encounters were made with a median duration of two minutes (interquartile range, 1–3). Number of contacts ranged from 25 to 49 encounters/8 h in the low-risk wards and 40 to 66 encounters/8 h in the high-risk wards. Physicians working during the 8-hour evening shift in high-risk wards had the highest estimated number of contacts (66 encounters; 95% confidence interval [CI], 43–89) while nurses working during the 8-hour night shift in the low-risk wards had the lowest number of contacts (25 encounters; 95% CI, 22–28). Forty-two (11%) shifts were staffed by HCPs with acute muscle pain and/or respiratory symptom(s) at the time of interview, and 89 (23%) by HCPs who reported symptom(s) during the past seven days, for which none were absent from work. Conclusion: We observed difference in encounter patterns by ward type. About one in five work shifts were staffed by HCPs with acute muscle pain and/or respiratory symptoms who continued to work while ill. These findings have implications for preventing infectious disease transmission and the policy around sick leave in healthcare settings. © 2022

BACKGROUND: We examined SARS-CoV-2 anti-spike 1 IgG antibody levels following COVID-19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer-BioNTech [PZ]) among Thai healthcare providers. METHODS: Blood specimens were tested using enzyme-linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ+1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV+1AZ, 2SV+1PZ). Differences in antibody levels were assessed using Kruskal-Wallis statistic, Mann-Whitney test, or Wilcoxon matched-pairs signed-rank test. Antibody kinetics were predicted using fractional polynomial regression. RESULTS: The 563 participants had median age of 39years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23days in both 1AZ and 2SV vaccinees and dropped below assay's cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55days among 1AZ vaccinees compared with 117days among 2SV vaccinees. 1AZ+1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1-4weeks post vaccination. 2SV+1PZ vaccinees had significantly higher antibody levels than 2SV+1AZ vaccinees 4weeks post vaccination (3423 vs. 2105 BAU/ml; p-value<0.01), and during weeks 5-8 (3656 vs. 1072 BAU/ml; p-value<0.01). Antibodies peaked at 12-15days in both 2SV+1PZ and 2SV+1AZ vaccinees, but those of 2SV+1AZ declined more rapidly and dropped below assay's cutoff in 228days while those of 2SV+1PZ remained detectable. CONCLUSIONS: 1AZ+1PZ, 2SV+1AZ, and 2SV+1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti-S1 IgG antibodies for possible protection against SARS-CoV-2 infection.

BACKGROUND: Pregnant women, healthcare workers (HW), and adults >= 60 years have shown an increased vulnerability to seasonal influenza virus infections and/or complications. In 2012, the Lao People's Democratic Republic (Lao PDR) initiated a national influenza vaccination program for these target groups. A cost-effectiveness evaluation of this program was undertaken to inform program sustainability. METHODS: We designed a decision-analytical model and collected influenza-related medical resource utilization and cost data, including indirect costs. Model inputs were obtained from medical record abstraction, interviews of patients and staff at hospitals in the national influenza sentinel surveillance system and/or from literature reviews. We compared the annual disease and economic impact of influenza illnesses in each of the target groups in Lao PDR under scenarios of no vaccination and vaccination, and then estimated the cost-effectiveness of the vaccination program. We performed sensitivity analyses to identify influential variables. RESULTS: Overall, the vaccination of pregnant women, HWs, and adults >= 60 years could annually save 11,474 doctor visits, 1,961 days of hospitalizations, 43,027 days of work, and 1,416 life-years due to laboratory-confirmed influenza illness. After comparing the total vaccination program costs of 23.4 billion Kip, to the 18.4 billion Kip saved through vaccination, we estimated the vaccination program to incur a net cost of five billion Kip (599,391 USD) annually. The incremental cost per life-year saved (ICER) was 44 million Kip (5,295 USD) and 6.9 million Kip (825 USD) for pregnant women and adults >= 60 years, respectively. However, vaccinating HWs provided societal cost-savings, returning 2.88 Kip for every single Kip invested. Influenza vaccine effectiveness, attack rate and illness duration were the most influential variables to the model. CONCLUSION: Providing influenza vaccination to HWs in Lao PDR is cost-saving while vaccinating pregnant women and adults >= 60 is cost-effective and highly cost-effective, respectively, per WHO standards.

BACKGROUND: Thailand was the first country outside China to report SARS-CoV-2 infected cases. Since the detection of the first imported case on January 12th, 2020 to the time this report was written, Thailand experienced two waves of community outbreaks (March-April 2020 and December 2020-March 2021). We examined prevalence of SARS-CoV-2 seropositivity among healthcare providers (HCPs) in four hospitals approximately one year after SARS-CoV-2 first detected in Thailand. By March 2021, these hospitals have treated a total of 709 coronavirus disease 2019 (COVID-19) patients. METHODS: Blood specimens, collected from COVID-19 unvaccinated HCPs during January-March 2021, were tested for the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies to nucleocapsid (IgG-nucleocapsid) and spike (IgG-spike) proteins using Euroimmune® enzyme-linked immunosorbent assays. RESULTS: Of 600 HCPs enrolled, 1 (0.2%) tested positive for the SARS-CoV-2 IgG-spike antibodies, but not the IgG-nucleocapsid. CONCLUSION: The presence of SARS-CoV-2 IgG antibodies was rare in this sample of HCPs, suggesting that this population remains susceptible to SARS-CoV-2 infection.

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.

Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries. Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression. Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value<0.01). Despite significant differences in sociodemographic characteristics in the three populations, most participants across sites who were aware of influenza prior to study enrollment believe they and their infants are at risk of influenza and related complications and believe influenza vaccination is safe and effective. Half of women in Lima had verified receipt of influenza vaccine compared to <5% in Bangkok and Nagpur (p < .05). For further analysis conducted among women in Lima only, household income above the poverty line (aOR: 1.38; 95%CI: 1.01, 1.88), having 8+ antenatal visits, compared to 0-4 (aOR: 2.41; 95%CI: 1.39, 2.87, respectively), having 0 children, compared to 2+ (aOR: 1.96; 95%CIs: 1.23, 3.12), and vaccination recommended by a health-care provider (aOR: 8.25; 95%CI: 6.11, 11.14) were strongly associated with receipt of influenza vaccine during pregnancy. Conclusions: Our findings identify opportunities for targeted interventions to improve influenza vaccine uptake among pregnant women in these settings.

BACKGROUND: We assessed performance of participant-collected mid-turbinate nasal swabs compared to study staff-collected mid-turbinate nasal swabs for the detection of respiratory viruses among pregnant women in Bangkok, Thailand. METHODS: We enrolled pregnant women aged ≥18 years and followed them throughout the 2018 influenza season. Women with acute respiratory illness (ARI) self-collected mid-turbinate nasal swabs at homes for influenza viruses, RSV, and hMPV real-time RT-PCR testing while the study nurse collected a second mid-turbinate nasal swab during home visits. Paired specimens were processed and tested on the same day. RESULTS: The majority (109, 60%) of 182 participants were 20-30 years old. All 200 paired swabs had optimal specimen quality. The median time from symptom onsets to participant-collected swabs was two days and to staff-collected swabs was also two days. The median time difference between the two swabs was two hours. Compared to staff-collected swabs, the participant-collected swabs were 93% sensitive and 99% specific for influenza virus detection, 94% sensitive and 99% specific for RSV detection, and 100% sensitive and 100% specific for hMPV detection. CONCLUSIONS: Participant-collected mid-turbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

BACKGROUND: We evaluated molecular-based point-of-care influenza detection systems in a laboratory prior to the field evaluations of on-site specimen testing. METHODS: Performance of 1) insulated isothermal PCR on the POCKIT(TM) device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96(TM) Real-time Detection System was used as a gold standard for comparisons. RESULTS: Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT(TM) only correctly identified influenza A(M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT(TM) was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini had mixed results depending on the types and subtypes of influenza viruses. CONCLUSIONS: The performance of the two systems in a laboratory is promising and supports further evaluation in field settings.

BACKGROUND: We compared cord blood antibody titers in unvaccinated pregnant women to those vaccinated with seasonal influenza vaccine during the 2(nd) and the 3(rd) trimesters. METHODS: Pregnant women had cord blood collected at delivery for hemagglutination inhibition assay against vaccine reference viruses: A/California/07/2009 (H1N1)pdm09, A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 (Yamagata lineage). Geometric mean titer (GMT) ratios were calculated comparing vaccinated versus unvaccinated pregnant women, and women vaccinated in the 2(nd) and the 3(rd) trimesters. Proportions of women achieving defined titers were compared using the χ(2) test. RESULTS: Of 307 women, 190 (62%) were unvaccinated. Fifty and 67 were vaccinated during the 2(nd) and the 3(rd) trimesters, respectively. Median enrollment age was 29 years (interquartile range 24-34). Sixteen (5%) women had pre-existing conditions, but none were immunocompromised. GMT ratios comparing vaccinated and unvaccinated women were 5.90 (95% confidence interval [CI] 5.06-6.96) for influenza A/California, 5.39 (95% CI 4.18-6.08) for influenza A/Switzerland, and 5.05 (95% CI 4.43-5.85) for influenza B/Phuket. Similarly, the GMT ratios comparing the 3(rd) and the 2(nd) trimester vaccinated women were 2.90 (95% CI 2.54-3.39), 2.82 (95% CI 2.56-3.13), and 2.83 (95% CI 2.56-3.14), respectively. The proportions of women with defined titers for the three vaccine reference viruses did not differ between 2(nd) and 3(rd) trimester vaccinated women (titers ≥40: 68-92% versus 70-93%; ≥110: 32% versus 33-63%; and ≥330: 4-10% versus 3-21%). CONCLUSIONS: Pregnant women vaccinated against influenza had more placental transfer of influenza antibodies to their infants than unvaccinated women. Placental transfer of antibodies was higher among those vaccinated in the 3(rd) trimester than in the 2(nd) trimester. There was no difference in the proportions of women achieving antibody titers corresponding to protection against influenza in children. Findings support the current World Health Organization's recommendation that pregnant women may be vaccinated in either 2(nd) or 3(rd) trimester of pregnancy.

BACKGROUND: The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, though their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. METHODS: In 2017 and 2018, we contacted 11,277 pregnant women twice weekly during the influenza season to identify illnesses with new or worsened cough, runny nose, sore throat, difficulty breathing or myalgia, and collected data on other symptoms and nasal swabs for influenza rRT-PCR testing. We calculated sensitivity, specificity, positive predictive value and negative predictive value of each symptom-predictor, WHO respiratory illness case definitions and a de novo definition derived from results of multivariable modelling. RESULTS: Of 5,444 eligible illness episodes among 3,965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever ≥38° Celsius (adjusted odds ratio = 4.6, 95% confidence interval [CI] = 3.1, 6.8), myalgia (3.0, 95% CI: 2.2, 4.0), cough (2.7, 95% CI: 1.9, 3.9), and chills (1.6, 95% CI: 1.1, 2.4) were independently associated with influenza illness. A definition based on these four (measured fever, cough, chills or myalgia), was 95% sensitive and 27% specific. The WHO influenza-like illness (ILI) definition was 16% sensitive and 98% specific. CONCLUSIONS: The current WHO ILI case definition was highly specific but had low sensitivity. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity.

BACKGROUND: Influenza vaccination during pregnancy prevents influenza among women and their infants but remains underused among pregnant women. We aimed to quantify the risk of antenatal influenza and examine its association with perinatal outcomes. METHODS: We did a prospective cohort study in pregnant women in India, Peru, and Thailand. Before the 2017 and 2018 influenza seasons, we enrolled pregnant women aged 18 years or older with expected delivery dates 8 weeks or more after the season started. We contacted women twice weekly until the end of pregnancy to identify illnesses with symptoms of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing and collected mid-turbinate nasal swabs from symptomatic women for influenza real-time RT-PCR testing. We assessed the association of antenatal influenza with preterm birth, late pregnancy loss (≥13 weeks gestation), small for gestational age (SGA), and birthweight of term singleton infants using Cox proportional hazards models or generalised linear models to adjust for potential confounders. FINDINGS: Between March 13, 2017, and Aug 3, 2018, we enrolled 11 277 women with a median age of 26 years (IQR 23-31) and gestational age of 19 weeks (14-24). 1474 (13%) received influenza vaccines. 310 participants (3%) had influenza (270 [87%] influenza A and 40 [13%] influenza B). Influenza incidences weighted by the population of women of childbearing age in each study country were 88·7 per 10 000 pregnant woman-months (95% CI 68·6 to 114·8) during the 2017 season and 69·6 per 10 000 pregnant woman-months (53·8 to 90·2) during the 2018 season. Antenatal influenza was not associated with preterm birth (adjusted hazard ratio [aHR] 1·4, 95% CI 0·9 to 2·0; p=0·096) or having an SGA infant (adjusted relative risk 1·0, 95% CI 0·8 to 1·3, p=0·97), but was associated with late pregnancy loss (aHR 10·7, 95% CI 4·3 to 27·0; p<0·0001) and reduction in mean birthweight of term, singleton infants (-55·3 g, 95% CI -109·3 to -1·4; p=0·0445). INTERPRETATION: Women had a 0·7-0·9% risk of influenza per month of pregnancy during the influenza season, and antenatal influenza was associated with increased risk for some adverse pregnancy outcomes. These findings support the added value of antenatal influenza vaccination to improve perinatal outcomes. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Thai, Hindi, Marathi and Spanish translations of the abstract see Supplementary Materials section.

Despite recommendations, few children aged 6-35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012-2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years.

BACKGROUND: We measured seroconversion to influenza viruses and incidence of symptomatic influenza virus infection in a cohort of children in Bangkok, Thailand. METHODS: Children aged </=6 months were followed for two years for acute respiratory illness and had serum specimens taken at 6-month intervals and tested by hemagglutination inhibition (HI) assay. Seroconversion was defined as a >4-fold rise in the HI titers between time points with a titer of >40 in the second specimen. Respiratory swabs were tested by rRT-PCR for influenza. Data were analyzed using generalized linear models. RESULTS: Of 350 children, 266 (76%, 147 were healthy and 119 high-risk) had >/=2 serum specimens collected before influenza vaccination. During the 2-year follow-up, 266 children contributed 370 person-years of observation, excluding post-vaccination periods. We identified 32 ARI cases with rRT-PCR-confirmed influenza virus infection (7 infections/100 person-years, 95% confidence interval [CI], 4-11). There were 126 episodes of influenza virus infection, resulting in a seroconversion rate of 35 infections/100 person-years (95% CI, 30-42). Rates in healthy and high-risk children did not differ. CONCLUSIONS: Influenza virus infection is common during the first two years of life among Thai children. A large proportion of infections may not be detected using the ARI case definition.

BACKGROUND: Physician recommendation and attitudes and beliefs of pregnant women toward influenza and vaccination may influence vaccine uptake during pregnancy. We examined how physician recommendation and health beliefs of pregnant women may jointly affect influenza vaccination during pregnancy. METHODS: Thai pregnant women aged >/=18 years and >13 gestational weeks attending antenatal care (ANC) clinics, and ANC physicians were recruited during May-August 2015. Women and physicians, linked using unique identifiers, provided data on demographic, health and work history, knowledge, attitudes, and beliefs toward influenza and vaccination, based on Health Belief Model constructs. Physicians also provided data on their practices in recommending influenza vaccination during pregnancy. Prevalence ratios for the association between knowledge, attitudes and beliefs of pregnant women, physician recommendation and documented receipt of vaccination within 30 days of the visit were calculated. RESULTS: Among 610 women, the median age was 27 years; 266 (44%) and 344 (56%) were in the second and third trimesters, respectively. Twenty-one (3%) had pre-existing conditions. Of 60 physicians with the median years of practice of 5; 17 (28%) reported frequently/usually/always recommending influenza vaccine to their pregnant patients, while 43 (72%) reported never/rarely/sometimes recommending the vaccine. Controlling for the pregnant women's knowledge and beliefs, pregnant women whose physician recommended influenza vaccination were 2.3 times (95% confidence interval 1.4-3.8) more likely to get vaccinated. CONCLUSIONS: In this study, physician recommendation was the only significant factor associated with influenza vaccine uptake among Thai pregnant women. Understanding physicians' motivation/barrier to recommending influenza vaccination to pregnant women may increase coverage.

BACKGROUND: The World Health Organization identifies pregnant women as at high-risk for severe influenza, but influenza vaccines are underutilized among pregnant women. Data on influenza burden during pregnancy are largely limited to high-income countries and data on the impact of influenza on birth and perinatal outcomes are scarce. METHODS/DESIGN: This prospective, longitudinal cohort study of pregnant women in middle-income countries is designed to address three primary objectives: 1) to evaluate the effect of laboratory-confirmed influenza during pregnancy on pregnancy and perinatal outcomes; 2) to estimate the incidences of all-cause acute respiratory illness and laboratory-confirmed influenza during pregnancy; and 3) to examine the clinical spectrum of illness associated with influenza viruses. Through a multi-country network approach, three sites aim to enroll cohorts of 1500-3000 pregnant women just before local influenza seasons. Women aged >/= 18 years with expected delivery dates >/= 8 weeks after the start of the influenza season are eligible. Women are followed throughout pregnancy through twice weekly surveillance for influenza symptoms (>/= 1 of myalgia, cough, runny nose, sore throat, or difficulty breathing) and have mid-turbinate nasal swabs collected for influenza virus testing during illness episodes. Primary outcomes include relative risk of preterm birth and mean birth weight among term singleton infants of women with and without reverse transcription polymerase chain reaction-confirmed influenza during pregnancy. Gestational age is determined by ultrasound at < 28 weeks gestation and birth weight is measured by digital scales using standardized methods. Sites are primarily urban in Bangkok, Thailand; Lima, Peru; and Nagpur, India. All sites recruit from antenatal clinics at referral hospitals and conduct surveillance using telephone calls, messaging applications, or home visits. Nasal swabs are self-collected by participants in Thailand and by study staff in Peru and India. During the first year (2017), sites enrolled participants during March-May in Peru and May-July in India and Thailand; 4779 women were enrolled. DISCUSSION: This study aims to generate evidence of the impact of influenza during pregnancy to inform decisions by Ministries of Health, healthcare providers, and pregnant women in middle-income countries about the value of influenza vaccination during pregnancy.

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.

BACKGROUND: Thailand recommends influenza vaccination among pregnant women. We conducted a cohort study to determine if the prevalence of adverse events following immunization (AEFIs) with influenza vaccine among Thai pregnant women was similar to that often cited among healthy adults. METHODS: Women who were >/=17 gestational weeks and >/=18 years of age were recruited. Demographic and health history data were collected using structured questionnaires. Women were provided with symptom diary, ruler to measure local reaction(s), and thermometer to measure body temperature. AEFIs were defined as any new symptom/abnormality occurring within four weeks after vaccination. The diaries were abstracted for frequency, duration, and level of discomfort/inconvenience of the AEFIs. Serious adverse events (SAEs) and the likelihood of AEFIs being associated with vaccination were determined using standard definitions. RESULTS: Among 305 women enrolled between July-November 2015, median age was 29 years. Of these, 223 (73%) were in their third trimester, 271 (89%) had completed secondary school or higher, and 20 (7%) reported >/=1 pre-existing conditions. AEFIs were reported in 134 women (44%; 95% confidence interval [CI] 38-50%). Soreness at the injection site (74, 24%; CI 19-29%), general weakness (50, 16%; CI 12-21%), muscle ache (49, 16%; CI 12-21%), and headache (45, 15%; CI 1-19%) were most common. Of those with AEFIs, 120 (89%) reported symptom/abnormality occurred on day 0 or day 1 following vaccination. Ten women (7%) reported the AEFIs affected daily activities. The AEFIs generally spontaneously resolved within 24 h of onset. There were two vaccine-unrelated SAEs. Of 294 women with complete follow-up, 279 (95%) had term deliveries, 12 (4%) had preterm deliveries, and 3 (1%) had miscarriage or stillbirth. CONCLUSION: In our cohort, AEFIs with influenza vaccine occurred with similar frequency to those reported among healthy adults in other studies, and were generally mild and self-limited. No influenza vaccine-associated SAEs were identified.

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 Thai Advisory Committee on Immunization Practices recommends annual influenza vaccination for children six months through two years of age, although older children may be vaccinated on request. We evaluated effectiveness of the 2013 and 2014 inactivated influenza vaccines to reduce medically-attended laboratory-confirmed influenza illness among Thai children aged 7-60 months. METHODS: From September 2013-May 2015, children with influenza-like illness (ILI) were screened with a rapid influenza diagnostic test. Enrolled children had nasal and throat swabs tested for influenza viruses using polymerase chain reaction (PCR). Cases and controls were subjects testing positive and negative, respectively, for influenza viruses by PCR. Vaccination status was ascertained from vaccination cards. Vaccine effectiveness (VE) was calculated as 100%*(1-odds ratio of vaccination among cases versus controls). RESULTS: Of 1,377 children enrolled, cases (n=490) and controls (n=887) were similar in demographic characteristics. Cases were less likely to receive influenza vaccine than controls in 2013 (6% vs. 14%; p=0.02), but not in 2014 (6% vs. 7%; p=0.57). Among cases, 126 (26%) were positive for influenza A(H1N1)pdm09 virus, 239 (49%) for influenza A(H3N2) and 124 (25%) for influenza B. One specimen was positive for both influenza A(H3N2) and B viruses. VE for full vaccination against all viruses was 64% (95% confidence interval [CI], 21%, 84%) in 2013 and 26% (95% CI, -47%, 63%) in 2014. CONCLUSIONS: Influenza vaccination was low among Thai children in our study, and VE varied by year, highlighting the need for annual monitoring of VE to better understand vaccine program effectiveness.

BACKGROUND: Each year, an influenza B strain representing only one influenza B lineage is included in the trivalent inactivated influenza vaccine (IIV3); a mismatch between the selected lineage and circulating viruses can result in sub-optimal vaccine effectiveness. We modeled the added potential public health impact of a quadrivalent inactivated influenza vaccine (IIV4) that includes strains from both influenza B lineages compared to IIV3 on influenza-associated morbidity and mortality in Thailand. METHODS: Using data on the incidence of influenza-associated hospitalizations and deaths, vaccine effectiveness, and vaccine coverage from the 2007-2012 influenza seasons in Thailand, we estimated rates of influenza-associated outcomes that might be averted by using IIV4 instead of IIV3. We then applied these rates to national population estimates to calculate averted illnesses, hospitalizations, and deaths for each season. We assumed that the influenza B lineage included in IIV3 would provide a relative vaccine effectiveness of 75% against the other B lineage.. RESULTS: Compared to use of IIV3, use of IIV4 might have led to an additional reduction ranging from 0.4 to 14.3 influenza-associated illnesses per 100,000 population/year, <0.1 to 0.5 hospitalizations per 100,000/year, and <0.1 to 0.4 deaths per 1,000/year. Based on extrapolation to national population estimates, replacement of IIV3 with IIV4 might have averted an additional 267 to 9,784 influenza-associated illnesses, 9 to 320 hospitalizations, and 0 to 3 deaths. CONCLUSION: Compared to use of IIV3, IIV4 has the potential to further reduce the burden of influenza-associated morbidity and mortality in Thailand. This article is protected by copyright. All rights reserved.

BACKGROUND: Since 2009, Thailand has recommended influenza vaccine for children aged 6 months through 2 years, but no estimates of influenza vaccine coverage or effectiveness are available for this target group. METHODS: During August 2011-May 2013, high-risk and healthy children aged ≤36 months were enrolled in a 2-year prospective cohort study. Parents were contacted weekly about acute respiratory illness (ARI) in their child. Ill children had combined nasal and throat swabs tested for influenza viruses by real-time reverse transcription-polymerase chain reaction. Influenza vaccination status was verified with vaccination cards. The Cox proportional hazards approach was used to estimate hazard ratios. Vaccine effectiveness (VE) was estimated as 100% x (1-hazard ratio). RESULTS: During 2011-2013, 968 children were enrolled (median age, 10.3 months); 948 (97.9%) had a vaccination record and were included. Of these, 394 (41.6%) had ≥1 medical conditions. Vaccination coverage for the 2011-2012 and 2012-2013 seasons was 29.3% (93/317) and 30.0% (197/656), respectively. In 2011-2012, there were 213 ARI episodes, of which 10 (4.6%) were influenza positive (2.3 per 1000 vaccinated and 3.8 per 1000 unvaccinated child-weeks). The VE was 55% (95% confidence interval [CI], -72, 88). In 2012-2013, there were 846 ARIs, of which 52 (6.2%) were influenza positive (1.8 per 1000 vaccinated and 4.5 per 1000 unvaccinated child-weeks). The VE was 64% (CI, 13%, 85%). CONCLUSION: Influenza vaccination coverage among young children in Thailand was low, although vaccination was moderately effective. Continued efforts are needed to increase influenza vaccination coverage and evaluate VE among young children in Thailand.

Rapid influenza diagnostic tests (RIDTs) are often used at point-of-care due to their ease of use and rapidly available results. Most tests are lateral flow immunoassays that detect chromatographic changes if an influenza antigen is present in the respiratory specimen. These tests have high specificity (therefore, a positive is almost certainly a true positive) but low sensitivity (therefore, will often miss true cases).1,2 A newer immunofluorescence assay, Sofia A+B FIA (Quidel, San Diego, CA), demonstrated increased sensitivity but maintained high specificity.3 However, on December 3, 2012, Quidel issued a voluntary recall of certain lots of Sofia A+B because of false positive results.4 | In August 2011, we began a prospective cohort study of children aged ≤36 months at Queen Sirikit National Institute of Child Health, the largest pediatric referral hospital in Thailand. Children (equal numbers of high risk and healthy) are followed for 2 years and parents contacted weekly to inquire about whether their child had acute respiratory illness. Ill children came to the hospital and had a combined nasal and throat swab collected and tested for influenza viruses by realtime reverse transcription polymerase chain reaction (rRT-PCR).5 In addition, a separate nasal swab was taken and tested using 1 of 2 RIDTs made by Quidel (QuickVue A+B during August 2011 to January 20, 2013; Sofia A+B during January 21, 2013 to May 2013). | Of the 1152 specimens tested with QuickVue A+B, 59 (5.1%) were positive by rRT-PCR. Compared with rRT-PCR, Quick-Vue A+B had a sensitivity of 55.9% (33/59; 95% confidence interval (CI): 42.4–68.8%) and a specificity of 99.4% (1086/1093; 95% CI: 98.7–99.7%). Seven (0.6%) were false positive on QuickVue A+B. Of the 370 specimens tested with Sofia A+B, 12 (3.2%) were positive by rRT-PCR. Compared with rRT-PCR, Sofia had a sensitivity of 100% (12/12; 95% CI: 73.5–100.0%) and a specificity of 61.2% (219/358; 95% CI: 55.9–66.3%). One-hundred thirty nine (38.8%) were false positive on Sofia. Of the 139 false positives, 123 (88.5%) were influenza B and 16 were influenza A. There was no difference in the time between illness onset and specimen collection date between true and false positives (median days = 2; P = 0.96), nor was there a difference between the prevalence of influenza during the 2 periods (5.1% vs. 3.2%, P = 0.1). Two lots of the Sofia assay were used and both had poor specificity (data not shown).

BACKGROUND: Tuberculin skin test (TST) identifies patients highly likely to benefit from isoniazid preventive therapy (IPT) and tuberculosis (TB) prevalence may differ by TST status. We evaluated latent and active TB screening and diagnosis strategies among people living with HIV (PLHIV) incorporating TST as the initial screening step. METHODS: PLHIV attending services at the Thai Red Cross Anonymous Clinic during September 2006-January 2008 were enrolled. TB disease was defined as any positive MTB specimen culture from sputum, urine, stool, lymph node aspiration, and blood. The performance of symptom screening (>1 of: any cough, any fever, night sweats lasting 3 or more weeks in the preceding 4 weeks) and laboratory screening (sputum smear followed by chest radiography and CD4 count) for active TB disease were evaluated according to TST status. RESULTS: We enrolled 604 PLHIV. TST was positive in 151 PLHIV (25.0%). TB disease was diagnosed in 33 PLHIV, including 22 (14.6%) TST-positive and 11 (2.4%) TST-negative PLHIV. We found that an approach of performing MTB culture for all TST-positive PLHIV and symptom screening followed by laboratory screening for all TST-negative PLHIV would identify 196 (32.4%) of 604 PLHIV who would need MTB culture to correctly diagnose 29 (87.9%) of 33 active TB cases. CONCLUSIONS: TST can be used as an initial screening test among PLHIV to identify those at highest risk of active TB disease. Access to MTB culture or other sensitive tests to exclude TB disease is urgently needed to improve TB screening and prevention in resource-limited settings.