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The prevalence of drug-resistant tuberculosis (DR-TB) in adults has stabilized in the past decade. Our study aimed to describe the prevalence of DR-TB in Thai children between 2006 and 2021.Children younger than 15 years old who had culture-confirmedAmong 163 confirmed TB cases (44% as pulmonary TB, 27% as extrapulmonary TB, and 29% with both), the median age (IQR) was 12.2 (7.3-14.2) years. DST was performed in 139 cases (85%), revealing prevalences of all DR-TB, isoniazid-resistant TB (Hr-TB), and rifampicin monoresistant/multidrug-resistant TB (Rr/MDR-TB) of 21.6% (95% CI 14.7-28.4), 10.8% (95% CI 5.6-16.0%), and 2.9% (95% CI 0.1-5.7%), respectively. The DR-TB rates did not differ significantly between 2006-2013, 2014-2018, and 2019-2021 (The prevalence of DR-TB in Thai children was stable. However, one-tenth of DR-TB cases confirmed with DST were Hr-TB, which required adjustment of the treatment regimen. The pre-XDR cases should be closely monitored.

Here, we describe the development of the in-house anti-Zika virus (ZIKV) IgM antibody capture ELISA (in-house ZIKV IgM ELISA) for the detection and diagnosis of acute ZIKV infections. We compared the in-house ZIKV IgM ELISA assay performance against two commercial kits, Euroimmun ZIKV IgM and InBios 2.0 ZIKV IgM ELISA. We tested the assays’ ability to detect anti-ZIKV IgM using a well-defined serum sample panel. This panel included 80 ZIKV negative samples (20 negative, 20 found to be primary dengue virus [DENV][ infections, 20 secondary DENV infections, and 20 Japanese encephalitis virus [JEV] infections) and 67 ZIKV reverse transcriptase–polymerase chain reaction–positive acute serum samples. The OD values were calculated to enzyme immunoassay (EIA) unts by comparing them to weak positive controls. The results demonstrated the high sensitivity (88.06%) and specificity (90.00%) of our in-house ZIKV IgM ELISA and its 89.12% overall percentage agreement. The kappa values were deemed to be within excellent range and comparable to the InBios ZIKV IgM ELISA. Some cross-reactivity was observed among secondary DENV and JEV samples, and to a much lower extent, among primary DENV samples. These data indicate that our in-house ZIKV IgM ELISA is a reliable assay for the detection of anti-ZIKV IgM antibodies in serum.

Background Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. Methods We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months–17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012–2013 to 2016–2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 – adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. Results We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7–10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012–2013 to 2016–2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. Conclusions Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

Background Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. Methods We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. Results Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P Conclusions Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.

Background To evaluate the impact of vitamin D and calcium supplementation (VitD/Ca) on lumbar spine bone mineral density (LSBMD) and bone metabolism among Thai adolescents with perinatally acquired HIV (PHIVA). Methods A multicenter, randomized, active-control, open-labeled trial was conducted. PHIVA (aged 10–20 years) who were on stable cART were enrolled. Baseline LSBMD status was defined as low (z-score ≤ −2) and normal (> −2). Eligible PHIVA were randomly assigned to receive standard-dose (400 IU/1200 mg/day) or high-dose (400 IU/1200 mg/day plus ergocalciferol 20 000 IU/week) VitD/Ca supplementation for 48 weeks (ratio 1:1, stratified by baseline LSBMD). Study outcomes were changes in LSBMD, LSBMD z-scores, and bone metabolism–related biomarkers (25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone [iPTH], C-terminal telopeptide [CTX], procollagen type I amino-terminal propeptide [PINP]) from baseline to week 48. Results Among 200 enrolled PHIVA, median age was 16 (IQR:14–18) years; 61% were on NNRTI-based cART. Median 25(OH)D level was 25.5 (IQR: 20.8–33.0) ng/mL. After 48-week VitD/Ca supplementation, LSBMD significantly increased in both treatment groups (high-dose: median: +0.07 [IQR: +0.04 to +0.11] g/cm2; P Conclusions Over 48-week VitD/Ca supplementation, significant increases in LSBMD, and significant decreases in bone metabolism–related markers were observed among our Thai PHIVA in both treatment groups. The improvement in LSBMD z-score was more enhanced with high-dose VitD/Ca supplementation than standard-dose. High-dose VitD/Ca supplementation might be considered to promote bone health in this population. Clinical Trials Registration NCT02426840.

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

Background We assessed performance of participant-collected midturbinate nasal swabs compared to study staff-collected midturbinate 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 self-collected midturbinate nasal swabs at home for influenza viruses, respiratory syncytial viruses (RSV), and human metapneumoviruses (hMPV) real-time RT-PCR testing and the study nurse collected a second midturbinate 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 2 days and to staff-collected swabs was also 2 days. The median time interval between the 2 swabs was 2 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 midturbinate 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: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection. Methods: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies. Results: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay. Conclusions: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.

Introduction Efavirenz (EFV) is commonly used for first‐line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48‐week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV‐ to RPV‐based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV. Methods We conducted an open‐label, single‐arm, multi‐centre study in Thailand in virologically suppressed adolescents aged 12–18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018. Results One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4–17.0), median CD4 count was 664 cells/mm3 (29.9%); 58% were receiving tenofovir‐DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV‐associated mutations (K101E and Y181C) and a lamivudine‐associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV‐related symptoms, depression score or health‐related QOL were observed over time; however, there was significant improvement in performance‐based assessments of executive function at week 24. Conclusions A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.

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

Combination antiretroviral drug regimens are increasingly preferred for neonatal postexposure prophylaxis (PEP) among HIV-exposed infants with high-risk of transmission. We evaluated the adverse events associated with the use of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) for neonatal PEP during the first 6 weeks of life.A prospective cohort of non-breast-fed HIV-exposed infants was conducted at 5 clinical sites in Thailand. Study population included 100 high-risk HIV-exposed infants (maternal HIV RNA50 copies/mL prior to delivery or received antiretroviral therapy less than 12 weeks) and 100 low-risk HIV-exposed neonates. High-risk infants received ZDV/3TC/NVP for 6 weeks whereas low-risk HIV-exposed neonates received a 4-week regimen of ZDV. Complete blood count, aspartate transaminase and alanine transaminase were assessed at birth, 1, 2 and 4 months of life.From October 2015 to November 2017, 200 infants were enrolled, of which 18.5% had low birth weight2500 g. The proportion of infants with anemia grade 2 or higher at 1 and 2 months of life between ZDV/3TC/NVP and ZDV prophylaxis was 48.5% vs 32.3% (P=0.02); nevertheless, severe anemia (grade 3) was not significantly different; 9.2% vs 10.2% (P=0.81), respectively. At 1 month old, infants on ZDV/3TC/NVP prophylaxis had significantly higher grade 2 anemia versus infants on ZDV alone (33.0% vs 13.4%; P=0.001); however, no difference was observed at 2 months old. No differences in neutropenia or hepatotoxicity between infant prophylactic regimens were observed.Triple antiretroviral neonatal PEP with ZDV/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with ZDV-monotherapy prophylaxis.

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.

Triple-drug infant antiretroviral prophylaxis containing nevirapine (NVP) is increasingly used to prevent HIV transmission among neonates at high risk of HIV infection. Our aim was to describe NVP concentration from birth through the first month of life.High-risk HIV-exposed neonates were enrolled in a prospective cohort in Thailand. High-risk neonates defined as maternal HIV RNA50 copies/mL before delivery or mother received antiretroviral treatment for12 weeks before delivery. Neonates received zidovudine (4 mg/kg) and lamivudine (2 mg/kg) twice daily, plus NVP (4 mg/kg) once daily (no lead-in) from birth to 6 weeks of life. Infant plasma samples were collected at 1, 2, 14 or 2, 7, 28 days of life. NVP trough concentrations (C24) were estimated using a population pharmacokinetic model and target C24 was ≥0.1 mg/L. "Washout" efavirenz (EFV) concentrations were assessed in infants whose mother received EFV-based antiretroviral treatment.A total of 48 infants were included: 25 (52%) were male and 12 (25%) were preterm (gestational age 34-37 weeks). Median (interquartile range) predicted NVP C24 were 1.34 mg/L (1.13-1.84), 2.24 (2.00-2.59), 2.78 (2.61-3.12), 2.20 (1.86-2.44) and 0.81 (0.58-0.98) on days 1, 2, 7, 14 and 28 of life, respectively. NVP C24 was not significantly different between term and preterm infants. All infants maintained NVP C24 ≥0.1 mg/L. EFV via placental transfer remained detectable in infants up to 7 days of life.NVP 4 mg/kg daily from birth provided adequate prophylactic concentrations during the first month of life in high-risk HIV-exposed neonates.

Background Diagnosing tuberculosis (TB) in children is challenging due to its paucibacillary nature. Loop-mediated isothermal amplification (TB-LAMP) is a simple, rapid, and specific point-of-care molecular diagnostic test. However, evaluation of its performance remains limited in children. This study aimed to evaluate the diagnostic performance of Eiken TB-LAMP among children with presumed tuberculosis disease. Methods Pulmonary and extrapulmonary specimens were collected from children under 18 years with presumed TB. Each specimen was tested by using TB-LAMP, acid-fast bacilli (AFB) smear microscopy, and one of the two molecular assays (polymerase chain reaction [PCR] or Xpert MTB/RIF). Sensitivity and specificity were estimated compared to mycobacterial culture as reference standard. Results From January 2020 to January 2021, 75 participants with presumed TB were enrolled with median age of 7 years (IQR 2-12). Seventeen specimens from 16 (21.3%) children had bacteriologically confirmed TB: 10 pulmonary and 7 extrapulmonary specimens. Overall sensitivity and specificity of TB-LAMP was 76.5% (95% CI 50.1%-93.2%) and 100% (95% CI 94.3%-100%), respectively. It had significantly higher sensitivity than AFB (52.9%, 95% CI 27.8%-77.0%) and similar to other molecular assays; PCR 82.4% (95% CI 56.6%-96.2%), Xpert MTB/RIF 70.0% (95% CI 34.8%-93.3%). Sensitivity of TB-LAMP for pulmonary, lymph node tissue, and extrapulmonary fluid was 80% (95% CI 44.4%-97.5%), 100% (95% CI 39.8-100), and 33.3% (95% CI 0.8-90.6), respectively. TB-LAMP detected all smear-positive (N = 9) and 50% of smear-negative (N = 8) specimens. Conclusions TB-LAMP had higher sensitivity than AFB microscopy and accuracy similar to other molecular assays in both pulmonary and extrapulmonary specimens. These findings support using TB-LAMP as a point-of-care test in children.

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens., Phylogeographic analyses can provide broad descriptions of the spread of pathogens between populations, but are limited by incomplete sampling. Here, the authors develop an inference framework that reconstructs sequential transmission events and use it to characterise dynamics of dengue in Thailand.

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that reconstructs transmission across spatial scales and apply it to geocoded dengue virus sequences from Thailand (N=726 over 18 years). We find infected individuals spend 96% of their daytime hours in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining transmission. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable across pathogens.

The coding-complete genome sequences of 22 chikungunya virus strains collected from the 2018-2019 outbreak in Thailand are reported. All sequences belong to the East Central South African (ECSA) genotype and contain two mutations, E1:K211E and E2:V264A, which were previously shown to be associated with increased viral infectivity, dissemination, and transmission in Aedes aegypti., The coding-complete genome sequences of 22 chikungunya virus strains collected from the 2018–2019 outbreak in Thailand are reported. All sequences belong to the East/Central/South African (ECSA) genotype and contain two mutations, E1:K211E and E2:V264A, which were previously shown to be associated with increased viral infectivity, dissemination, and transmission in Aedes aegypti.

Objectives: To investigate the incidence, clinical characteristics and cost associated with pertussis in Thai children with persistent cough. Methods: A prospective study was conducted among children aged 0–18 years with persistent cough for ≥7 days with at least one of the following: paroxysm, inspiratory whooping, or post-tussive emesis. Nasopharyngeal swabs were obtained and tested for pertussis real time polymerase chain reaction (RT-PCR). Results: 19.6% of children (28 out of 143) had pertussis confirmed by RT-PCR, 75% of cases occurred in children who were too young to complete their primary series of vaccine. Paroxysm and post-tussive emesis were the most consistent clinical features, identified in 96% and 93% of cases, respectively, whooping was found in only 18%. Pertussis cases were more likely to have household cough contact (64% versus 30%, p

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 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 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.

To evaluate seroprotection of different dosing strategies of reduced-diphtheria-tetanus-toxoid vaccine (Td) for adults during a diphtheria outbreak in Thailand, we enrolled 160 healthcare workers and 161 adults aged 20–60 years old and measured diphtheria antitoxin (DAT) level before administration of a Td vaccine. We scheduled a second Td at 4–8 weeks and a third Td at 6–12 months interval. DAT was measured 4 weeks after each dose. DAT levels of ≥0.1 and ≥1 IU/mL were considered as seroprotective and long-term seroprotective. Persons achieving long-term seroprotection were not given a further dose. The baseline seroprotection rate was 32.6%, which increased to 87.1% (95% confidence interval, 83.4–90.8%) after one dose. The seroprotection rate increased slightly with additional doses. The immune response was lowest among persons 30–49 years of age. We suggest 1-dose Td for adults during a diphtheria outbreak, and a 2-dose series being considered for those born before 1980.

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.

Background. Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. Methods. The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1–59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. Results. A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (κ = 0.50) and between arbitrators was 84% (κ = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (κ = 0.25) and 48.5% (κ = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). Conclusions. Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process.

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. Â We evaluated the performance of symptom-based case definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. Methods In 2017, we contacted 4774 pregnant women twice a week 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. To identify symptom predictors of influenza, we used multivariable logistic regression with forward selection of symptoms significant in univariate analysis after controlling for country, chronic conditions, influenza vaccination, and time from symptom onset to swab collection. We calculated sensitivity and specificity of each symptom, WHO respiratory illness case definitions and a case definition based on significant predictors from the multivariable model. Results Of 2431 eligible illness episodes among 1,716 participants, 142 (5.8%) were positive for influenza. Among individual symptoms, runny nose was most sensitive and measured fever ≥ 38° Celsius was most specific (Figure 1). In a multivariable model, measured fever ≥ 38° Celsius [adjusted odds ratio = 3.8, 95% confidence interval [CI] = 2.0–7.2], cough [2.7, CI 1.6–4.7], chills [2.2, CI 1.2–3.8], and myalgia [1.2, CI 2.2, 5.3] were independently associated with influenza illness. A case definition based on these four (measured fever, cough, chills or myalgia), was 91%-sensitive and 37% specific. Sensitivity and specificity of case definitions varied (Figure 2). Conclusion While a case definition based on one or more of fever, chills, cough or myalgia is highly-sensitive and moderately specific among pregnant women, case definitions requiring measured or subjective fever may miss many influenza cases making them sub-optimal for studies of burden or vaccine efficacy. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity. Disclosures All authors: No reported disclosures.

Within a hand-washing clinical trial, we evaluated factors associated with fomite contamination in households with an influenza-infected child. Influenza virus RNA contamination was higher in households with low absolute humidity and in control households, suggesting that hand washing reduces surface contamination.

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged

Please cite this paper as: Simmerman et al. (2011) Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand. Influenza and Other Respiratory Viruses 5(4), 256–267 Background Evidence is needed on the effectiveness of non-pharmaceutical interventions (NPIs) to reduce influenza transmission. Methodology We studied NPIs in households with a febrile, influenza-positive child. Households were randomized to control, hand washing (HW), or hand washing plus paper surgical face masks (HW + FM) arms. Study nurses conducted home visits within 24 hours of enrollment and on days 3, 7, and 21. Respiratory swabs and serum were collected from all household members and tested for influenza by RT-PCR or serology. Principal Findings Between April 2008 and August 2009, 991 (16·5%) of 5995 pediatric influenza-like illness patients tested influenza positive. Four hundred and forty-two index children with 1147 household members were enrolled, and 221 (50·0%) were aged

Background Rational infection control guidance requires an improved understanding of influenza transmission. We studied households with an influenza-infected child to measure the prevalence of influenza contamination, the effect of hand washing, and associations with humidity and temperature. Methodology We identified children with influenza and randomly assigned their households to hand washing and control arms. Six common household surfaces and the fingertips of the index patient and symptomatic family members were swabbed. Specimens were tested by real-time reverse-transcription polymerase chain reaction (rRT-PCR), and specimens with positive results were placed on cell culture. A handheld psychrometer measured meteorological data. Results Sixteen (17.8%) of 90 households had influenza A-positive surfaces by rRT-PCR, but no viruses could be cultured. The fingertips of 15 (16.6%) of the index patients had results positive for influenza A, and 1 virus was cultured. Index patients with seasonal influenza infections shed more virus than did patients with pandemic influenza infection. Control households had a higher prevalence of surface contamination (11 [24.4%] of 45) than did hand washing households (5 [11.1%] of 45); prevalence risk difference (PRD), 13.3%; [95% confidence interval {CI}, −2.2% to 28.9%]; P = .09). Households in which the age of the index patient was ≤8 years had a significantly higher prevalence of contamination (PRD ,19.1%; 95% CI, 5.3% -32.9%; P = .02). Within the strata of households with secondary infections, an effect of lower absolute humidity is suggested (P = .07). Conclusions We documented influenza virus RNA contamination on household surfaces and on the fingertips of ill children. Homes with younger children were more likely than homes of older children to have contaminated surfaces. Lower absolute humidity favors surface contamination in households with multiple infections. Increased hand washing can reduce influenza contamination in the home.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials., Author summary Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective, and early recognition of severe dengue and timely supportive care remain the only means to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding deployment of such vaccines or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers, vaccine developers, and public health specialists to develop endpoints. After two working group meetings and discussions at international meetings, the Delphi methodology was used to clarify and further develop endpoints such that 70% or greater agreement was reached on most endpoint definitions including moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. The process identified areas for further evaluation and standardization within the context of ongoing clinical studies. The endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Objectives The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. Methods We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. Results One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8–11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7–32.6) months, their median CD4 percentage was 12% (4–20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3–5.2) log10 HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage 5 log10 copies/mL (OR 2.46; 95% CI 1.04–5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. Conclusions In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine.

Introduction Thailand recommends influenza vaccination for children aged 6 months to