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Background Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. Methods We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus–associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. Findings In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. Interpretation Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. Funding Bill & Melinda Gates Foundation.

Background: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. Methods: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. Results: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. Conclusions: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, seasonal vaccination (SV) is recommended. However, SV with trivalent influenza vaccine (TIV) can induce antibody and type-I interferon (IFN) responses, and the effect of anti-DM treatment on these responses is incompletely understood. We evaluated the antibody response and IFN-α expression in individuals with and without type 2 DM (T2DM) following SV, and examined the effects on anti-DM treatment. TIV elicited sero-protection in all groups, but antibody persistency was <8 months, except for the antibody response to B-antigens in non-DM. T2DM impaired the IgG avidity index, and T2DM showed a significantly decreased response against H1N1 and H3N2, in addition to delaying and reducing haemagglutination-inhibition persistency against influenza B-antigens in DM groups treated with metformin (Met-DM) or glibenclamide (GB-DM). Following TIV, the Met-DM and GB-DM groups exhibited reduced IFN-α expression upon stimulation with whole- and split-virion influenza vaccines. Suppression of IFN-α expression in the Met-DM group was associated with a reduction in the mechanistic target of rapamycin complex-1 pathway and impaired IgG avidity index. Thus, single-dose TIV each year might not be suitable for T2DM. Our data could aid the development of an efficacious influenza vaccine for T2DM.

Supplemental Digital Content is available in the text., Background: Pneumonia remains the leading cause of death among children

Background We compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women. Methods During 1st June– 30th September 2018, four groups of cohort participants—vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels. Results A total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs for influenza A(H1N1), A(H3N2), and B vaccine strains were not significantly different among all four groups (all p-values >0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values 0.05). Conclusions The 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.

We report two cases of coronavirus disease 2019 (COVID-19) in travellers from Wuhan, China to Thailand. Both were independent introductions on separate flights, discovered with thermoscanners and confirmed with RT-PCR and genome sequencing. Both cases do not seem directly linked to the Huanan Seafood Market in Hubei but the viral genomes are identical to four other sequences from Wuhan, suggesting early spread within the city already in the first week of January.

Background Human respiratory syncytial virus (RSV) causes illnesses among all age groups and presents a burden to healthcare services. To better understand the epidemiology and seasonality of RSV in different geographical areas, the World Health Organization (WHO) coordinated a pilot initiative to access the feasibility of establishing RSV surveillance using the existing Global Influenza Surveillance and Response System (GISRS) platform. Objectives To describe and compare RSV and influenza seasonality in countries in the northern andsouthern temperate, and tropics during the period January 2017 to April 2019. Methods Fourteen countries in six WHO regions participating in the GISRS were invited for the pilot. Hospitalized patients presenting with severe acute respiratory illness (SARI), SARI without fever and outpatients presenting with acute respiratory illness (ARI) were enrolled from January 2017 to April 2019. The expected minimum sample size was 20 samples per week, year-round, per country. Real-time RT-PCR was used to detect RSV and influenza viruses. Results were uploaded to the WHO FluMart platform. Results Annual seasonality of RSV was observed in all countries, which overlapped to a large extent with the influenza activity. In countries, in temperate regions RSV peaked in the autumn/winter months. In Egypt, a subtropical country, RSV activity peaked in the cooler season. In the tropical regions, RSV peaked during the rainy seasons. Conclusion Early findings from the WHO RSV surveillance pilot based on the GISRS suggest annual seasonal patterns for of RSV circulation that overlap with influenza. RSV surveillance needs to be continued for several more seasons to establish seasonality patterns to inform prevention and control strategies.

BACKGROUND Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. OBJECTIVES Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. METHODS Patients with influenza-like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset

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.

Background Self-collection of nasal swabs could improve the timeliness of influenza virus detection in older adults. Objectives Measure the acceptability, adequacy, timeliness and validity of self-collected nasal swabs among adults ≥65 years in Thailand. Methods Our evaluation consisted of two parts: a one-month study among randomly-selected, community-dwelling older adults to simulate community-based surveillance for acute respiratory infections (ARI); and a clinic study of older adults with ARI to evaluate the sensitivity and specificity of self-collected nasal swabs for influenza virus infection compared with healthcare worker (HCW)-collected nasal and nasopharyngeal swabs. Results In the community study, 24% of participants experienced an ARI during the observation period. All (100%) participants with an ARI self-collected nasal swabs within 72 hours of symptom onset of which 92% were considered adequate samples. In the clinic study, 45% of patients with ARI presented within 72 hours of symptom onset. The sensitivity of self-collected nasal swabs for detection of influenza virus infection was 78% (95% CI 40-97) compared to nasopharyngeal and 88% (95% CI 47-100) compared to nasal swabs collected by HCW. Specificity was 100% (95% CI 97-100) compared to both methods. Self-collection of nasal swabs was found acceptable by 99% of participants in both studies. Conclusions Self-collection of nasal swabs was acceptable to older adults in Thailand who were able to take adequate samples. Self-collection of nasal swabs may improve the timeliness of sample collection but lower sensitivity will need to be considered. This article is protected by copyright. All rights reserved.

Clinical practice guidelines for influenza have been implemented to maximise the appropriate use of empirical oseltamivir; however, good predictive values are required.Between October 2011 and September 2013, children aged 15 years who presented at the Bamrasnaradura Infectious Diseases Institute with an influenza-like illness plus either (i) pneumonia or (ii) being in a higher risk group for influenza complications were prospectively enrolled. Respiratory specimens were taken for real-time polymerase chain reaction testing (RT-PCR). Clinical characteristics, laboratory data and oseltamivir therapy were recorded.85 cases were enrolled. Of these, the proportions of those with pneumonia, who were aged 2 years and who had underlying diseases were 74.1%, 56.5% and 38.8%, respectively. RT-PCR detected respiratory syncytial virusamong (35.3%), influenza (22.3by%), adenovirus (14.1%), human metapneumovirus (5.9%), para-influenza (3.5%) and no viruses (25.9 %). Pneumonia (OR 0.16, 95% CI 0.05-0.50) and having two clinical criteria (OR 0.24, 95% CI 0.08-0.76) were significantly negative predictors of influenza. Having cluster transmissions (OR 5.18, 95% CI 1.38-19.37) and a monocyte proportion7% (OR 3.58, 95% CI 1.15-11.17) were significantly positive predictors of influenza. The mean (SD) percentage of influenza-like illness during the study period was 7.04 (2.02).Clinical criteria guidelines yielded a low predictive value (22.3%) for influenza in children. Seasonality, cluster transmission, white blood cell and differential counts may be helpful in diagnosing influenza. Nonetheless, empirical oseltamivir should not be delayed for those in need.

Background The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. Methods Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. Results Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged

Background Influenza-associated mortality in subtropical or tropical regions, particularly in developing countries, remains poorly quantified and often underestimated. We analyzed data in Thailand, a middle-income tropical country with good vital statistics and influenza surveillance data. Methods We obtained weekly mortality data for all-cause and three underlying causes of death (circulatory and respiratory diseases, and pneumonia and influenza), and weekly influenza virus data, from 2006 to 2011. A negative binomial regression model was used to estimate deaths attributable to influenza in two age groups ( 65 years. The average annual rate of influenza-associated deaths was 0·7 (95% CI: −8·2 to 10) per 100 000 population for person aged

Background On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. Materials and methods We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. Results We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0–74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80–0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. Conclusions Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. Trial registration ClinicalTrial.gov, NCT04122222.

To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator.Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries.Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator.Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.Caractériser la saisonnalité de la grippe et identifier le meilleur moment de l'année pour la vaccination contre la grippe dans les pays tropicaux et subtropicaux de l'Asie du Sud et de l'Asie du Sud-Est, qui sont situés au nord de l'équateur.Les données hebdomadaires de la surveillance de la grippe pour la période allant de 2006 à 2001 ont été obtenues auprès du Bangladesh, du Cambodge, de l'Inde, de la République démocratique populaire lao, de la Malaisie, des Philippines, de Singapour, de la Thaïlande et du Viet Nam. Les taux hebdomadaires de l'activité grippale étaient basés sur le pourcentage de tous les échantillons nasopharyngés collectés au cours de l'année et dont les tests étaient positifs au virus de la grippe ou à l'acide nucléique viral au cours d'une semaine donnée. Les pourcentages de cas positifs mensuels ont été ensuite calculés pour définir les pics annuels de l'activité grippale au sein de chaque pays et entre les pays.L'activité grippale atteint son pic entre les mois de juin/juillet et octobre dans sept pays, parmi lesquels trois pays ont présenté un second pic entre les mois de décembre et février. Les pays proches de l'équateur présentent une circulation continue sans pic distinct. Les types et sous-types viraux varient d'une année à l'autre, mais pas entre les pays au cours d'une année donnée. Le pourcentage cumulatif des prélèvements dont les tests étaient positifs de juin à novembre, était supérieur à 60% au Bangladesh, au Cambodge, en Inde, en République démocratique populaire lao, aux Philippines, en Thaïlande et au Viet Nam. Par conséquent, ces pays tropicaux et subtropicaux ont enregistré plus tôt des pics d'activité grippale que dans les pays à climat tempéré situés au nord de l'équateur.La plupart des pays de l'Asie du Sud et de l'Asie du Sud-Est, situés au nord de l'équateur, devraient envisager la vaccination contre la grippe pendant la période allant d'avril à juin. Les pays proches de l'équateur sans pic distinct d'activité grippale peuvent baser leur calendrier de vaccination sur leurs facteurs locaux.Describir la estacionalidad de la gripe e identificar el mejor momento del año para llevar a cabo la vacunación contra la gripe en países tropicales y subtropicales del sur y sureste de Asia situados al norte del ecuador.Se obtuvieron los datos semanales de vigilancia de la gripe de los años 2006 a 2011 de Bangladesh, Camboya, India, Indonesia, la República Democrática Popular Lao, Malasia, Filipinas, Singapur, Tailandia y Viet Nam. Las tasas semanales de la actividad de la gripe se basaron en el porcentaje de todas las muestras nasofaríngeas recogidas durante el año que dieron positivo en la prueba del virus de la gripe o del ácido nucleido viral en cualquier semana. Los índices de resultados positivos mensuales se calcularon luego a fin de determinar los picos anuales de la actividad de la gripe en cada uno de los países y entre países.La actividad de la gripe experimentó un aumento entre junio y julio, y octubre en siete países, tres de los cuales mostraron un segundo pico de actividad de diciembre a febrero. Los países más cercanos al ecuador presentaron una circulación durante todo el año sin picos discontinuos. Los tipos y subtipos virales variaron de año en año, pero no entre los países en un año determinado. La proporción acumulada de individuos que dieron positivo de junio a noviembre fue 60 % en Bangladesh, Camboya, India, la República Democrática Popular Lao, Filipinas, Tailandia y Viet Nam. Así, en estos países tropicales y subtropicales, los picos de actividad de la gripe se produjeron antes que en los países de clima templado al norte de la línea ecuatorial.La mayoría de los países del sur y sureste asiático situados al norte del ecuador deberían considerar llevar a cabo la vacunación contra la gripe de abril a junio; mientras que los países cercanos al ecuador sin picos marcados en la actividad de la gripe pueden basar la fecha de vacunación en factores locales.تحديد خصائص موسمية الأنفلونزا والتعرف على أفضل أوقات السنة للتطعيم ضد الأنفلونزا في البلدان المدارية ودون المدارية في جنوب وجنوب شرق آسيا الواقعة شمال خط الاستواء.تم الحصول على بيانات الترصد الأسبوعية للأنفلونزا للفترة من 2006 إلى 2011 من بنغلاديش وكمبوديا والهند وإندونيسيا وجمهورية لاو الديمقراطية الشعبية وماليزيا والفلبين وسنغافورة وتايلند وفييت نام. واستندت المعدلات الأسبوعية لنشاط الأنفلونزا على النسبة المئوية لجميع عينات البلعوم الأنفي التي تم جمعها أثناء العام والتي كانت نتائج اختباراتها إيجابية لفيروس الأنفلونزا أو الحمض النووي الفيروسي في أسبوع معين. وتم حساب معدلات الإيجابية الشهرية لتحديد فترات ذروة نشاط الأنفلونزا السنوية في كل بلد وعبر البلدان.بلغ نشاط الأنفلونزا ذروته في الفترة بين حزيران/يونيو / تموز/يوليو وتشرين الأول/أكتوبر في سبعة بلدان، حيث أظهرت ثلاثة منها ذروة ثانية في الفترة من كانون الأول/ديسمبر إلى شباط/فبراير. وشهدت البلدان الأقرب إلى خط الاستواء دوراناً طوال العام دون فترات ذروة منفصلة. واختلفت الأنماط والأنماط الفرعية للفيروس من سنة إلى أخرى، ولكن لم تختلف عبر البلدان في سنة معينة. وكانت النسبة التراكمية للعينات التي كانت نتائج اختباراتها إيجابية من حزيران/يونيو إلى تشرين الثاني/نوفمبر أكبر من 60 % في بنغلاديش وكمبوديا والهند وجمهورية لاو الديمقراطية الشعبية والفلبين وتايلند وفييت نام. ومن ثم، أظهرت هذه البلدان المدارية ودون المدارية فترات ذروة مبكرة لنشاط الأنفلونزا عن البلدان معتدلة المناخ الواقعة شمال خط الاستواء.ينبغي أن تنظر معظم بلدان جنوب وجنوب شرق آسيا الواقعة شمال خط الاستواء في التطعيم ضد الأنفلونزا في الفترة من نيسان/إبريل إلى حزيران/يونيو؛ في حين تستطيع البلدان القريبة من خط الاستواء التي لا تشهد ذروة منفصلة في نشاط الأنفلونزا تحديد توقيت التطعيم على أساس العوامل المحلية.表征赤道以北的南亚和东南亚热带和亚热带国家流感季节性特点并确定流感疫苗接种最佳时间。从孟加拉国、柬埔寨、印度、印度尼西亚、老挝、马来西亚、菲律宾、新加坡、泰国和越南收集2006年至2011年的每周流感监测数据。每周流感活动率基于的是任何给定周测试流感病毒或病毒核酸阳性的一年中收集的鼻咽样本的百分比。然后,计算每月阳性率来定义每个国家和各国之间年流感活动的峰值。七个国家中,6月/7月和10月之间出现流感活动峰值,其中三个国家在12月至2月出现第二次峰值。靠近赤道的国家长年流感传播,没有不连续的峰值。病毒类型和子类型因年份而异,但在给定年份的各个国家之间没有变化。孟加拉国、柬埔寨、印度、老挝人民民主共和国、菲律宾、泰国和越南6月至11月测试阳性的样本的累积比例 60%。因此,较之赤道以北温带气候国家,这些热带和亚热带国家出现流感活动峰值更早。赤道以北的大多数亚洲南部和东南部国家应考虑从4月到6月接种流感疫苗,赤道附近没有出现明显的流感活动峰值的国家可以根据当地因素确定疫苗接种时间。Охарактеризовать сезонность гриппа и определить лучшее время года для проведения вакцинации против гриппа в тропических и субтропических странах Южной и Юго-Восточной Азии, расположенных к северу от экватора.Еженедельные данные эпиднадзора по гриппу с 2006 по 2011 гг. были получены из Бангладеш, Камбоджи, Индии, Индонезии, Лаосской Народно-Демократической Республики, Малайзии, Филиппин, Сингапура, Таиланда и Вьетнама. Недельные показатели активности гриппа вычислялись на основе процента от общего количества всех мазков из носоглотки, собранных в течение года, показавших положительный результат на вирус гриппа или вирусную нуклеиновую кислоту в течение любой данной недели. Затем были рассчитаны месячные показатели позитивности с целью определить ежегодные пики активности гриппа в каждой из стран и во всех странах региона.Активность гриппа достигала своего пика между июнем/июлем и октябрем в семи странах, в трех из которых отмечен второй пик с декабря по февраль. Страны ближе к экватору имели круглогодичную циркуляцию заболевания без отдельных пиков. Вирусные типы и подтипы менялись из года в год, но не во всех странах в отдельно взятом году. Совокупная доля положительных образцов с июня по ноябрь составила60% в Бангладеш, Камбодже, Индии, Лаосской Народно-Демократической Республики, Филиппинах, Таиланде и Вьетнаме. Таким образом, эти тропические и субтропические страны показали более ранние пики активности гриппа по сравнению со странами с умеренным климатом к северу от экватора.Большинству стран Южной и Юго-Восточной Азии, расположенных к северу от экватора, следует рассмотреть проведение вакцинации против гриппа в сроки с апреля по июнь; страны вблизи экватора без четко выраженного пика активности гриппа могут определять сроки вакцинации исходя из местных факторов.

Background Inactivated influenza vaccine (IIV) effectiveness has been evaluated among older adults in high-income countries, but data on IIV effectiveness in low- and middle-income countries remain sparse. We conducted a test-negative case–control analysis to estimate 2010 and 2011 trivalent IIV effectiveness against hospitalization with influenza-associated acute respiratory infection (ARI) among persons aged ≥50 years in rural Thailand. Methods During 2010–2011, active surveillance for ARI hospitalization was conducted in two provinces; patients were tested for influenza viruses by real-time RT-PCR. Vaccination status was obtained from vaccine registries. Case and control patients were patients with nasopharyngeal swabs positive and negative for influenza viruses, respectively. Vaccine effectiveness (VE) was estimated for the 6 months after vaccination began. Logistic regression was used to evaluate the association between case status and vaccination while adjusting for age, province, medical conditions, and time. Results During 2010–2011, there were 1545 patients with ARI, of whom 279 (18%) were influenza-positive case patients and 1266 (82%) were influenza-negative control patients. Of the 279 case patients, 247 (89%) had influenza A and 32 (11%) had influenza B. Fourteen of 279 (5%) case patients and 108 of 1266 (9%) control patients were vaccinated against influenza. The unadjusted IIV effectiveness against hospitalization with influenza-associated ARI was 43% (95% CI: 0–68%); adjusted VE was 47% (95% CI: 5–71%). Conclusion The 2010 and 2011 IIVs were moderately effective against hospitalization with influenza-associated ARI among Thais aged ≥50 years, but IIV coverage was low. Additional efforts are warranted in Thailand to improve IIV uptake in this target group.

Pneumonia remains a leading cause of under-five morbidity and mortality globally. Comprehensive incidence, epidemiologic and etiologic data are needed to update prevention and control strategies.We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory tract infections (ALRI) among children5 years of age in rural Thailand. ALRI cases were systematically sampled for an etiology study that tested nasopharyngeal specimens by polymerase chain reaction; children without ALRI were enrolled as controls from outpatient clinics.We identified 28,543 hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs, 76% had findings consistent with pneumonia as identified by 2 study radiologists. The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95% confidence interval: 5707, 5837) and was higher in boys versus girls (incidence rate ratio 1.38, 95% confidence interval: 1.35-1.41) and in children 6-23 months of age versus other age groups (incidence rate ratio 1.76, 95% confidence interval: 1.69-1.84). Viruses most commonly detected in ALRI cases were respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and influenza viruses (8%). Compared with controls, ALRI cases were more likely to test positive for respiratory syncytial virus, influenza, adenovirus, human metapneumovirus and parainfluenza viruses 1 and 3 (P ≤ 0.01 for all). Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal Salmonella, accounted for 1.8% of cases.Our findings underscore the high burden of hospitalization for ALRI and the importance of viral pathogens among children in Thailand. Interventions targeting viral pathogens coupled with improved diagnostic approaches, especially for bacteria, are critical for better understanding of ALRI etiology, prevention and control.

Background Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear. Methods Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center. Results RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya. Conclusions Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.

Despite greater than 99% of influenza A viruses circulating in the Asia-Pacific region being resistant to the adamantane antiviral drugs in 2011, the large majority of influenza A (>97%) and B strains (∼99%) remained susceptible to the neuraminidase inhibitors oseltamivir and zanamivir. However, compared to the first year of the 2009 pandemic, cases of oseltamivir-resistant A(H1N1)pdm09 viruses with the H275Y neuraminidase mutation increased in 2011, primarily due to an outbreak of oseltamivir-resistant viruses that occurred in Newcastle, as reported in Hurt et al. (2011c, 2012a), where the majority of the resistant viruses were from community patients not being treated with oseltamivir. A small number of influenza B viruses with reduced oseltamivir or zanamivir susceptibility were also detected. The increased detection of neuraminidase inhibitor resistant strains circulating in the community and the detection of novel variants with reduced susceptibility are reminders that monitoring of influenza viruses is important to ensure that antiviral treatment guidelines remain appropriate.

Influenza epidemiology differs substantially in tropical and temperate zones, but estimates of seasonal influenza mortality in developing countries in the tropics are lacking. We aimed to quantify mortality due to seasonal influenza in Thailand, a tropical middle-income country. Time series of polymerase chain reaction-confirmed influenza infections between 2005 and 2009 were constructed from a sentinel surveillance network. These were combined with influenza-like illness data to derive measures of influenza activity and relationships to mortality by using a Bayesian regression framework. We estimated 6.1 (95% credible interval: 0.5, 12.4) annual deaths per 100,000 population attributable to influenza A and B, predominantly in those aged ≥60 years, with the largest contribution from influenza A(H1N1) in 3 out of 4 years. For A(H3N2), the relationship between influenza activity and mortality varied over time. Influenza was associated with increases in deaths classified as resulting from respiratory disease (posterior probability of positive association, 99.8%), cancer (98.6%), renal disease (98.0%), and liver disease (99.2%). No association with circulatory disease mortality was found. Seasonal influenza infections are associated with substantial mortality in Thailand, but evidence for the strong relationship between influenza activity and circulatory disease mortality reported in temperate countries is lacking.

Background The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. Methods and Findings We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (, The substantial global burden of influenza infections in children is revealed by Lafond and colleagues. Children in developing countries are 3 times more likely to be hospitalised and treatments vary. This study highlights the need for vaccination programs in the young., Editors' Summary Background Acute lower respiratory infections—bacterial and viral infections of the lungs and airways (the tubes that take oxygen-rich air to the lungs)—are major causes of illness and death in children worldwide. Pneumonia (infection of the lungs) alone is responsible for 15% of deaths among children under five years old and kills nearly one million young children every year. Globally, infections with respiratory syncytial virus and with Streptococcus pneumoniae are associated with about 25% and 18.3%, respectively, of all episodes of severe respiratory infection in young children. Another infectious organism that contributes to the global burden of respiratory disease among children is the influenza virus. Every year, millions of people become infected with this virus, which infects the airways and causes symptoms that include a high temperature, tiredness and weakness, general aches and pains, and a dry chesty cough. Most infected individuals recover quickly, but seasonal influenza outbreaks (epidemics) nevertheless kill about half a million people annually, with the highest burden of severe disease being experienced by elderly people and by children under five years old. Why Was This Study Done? Annual immunization (vaccination) can reduce an individual’s risk of catching influenza, but before a country implements this preventative measure, policymakers need reliable estimates of the burden of influenza in their country. Although such estimates have been calculated for resource-rich countries with temperate climates, where influenza largely occurs in the winter, few estimates of influenza burden are available for resource-limited countries, which has hampered informed consideration of vaccination for influenza prevention in many settings. Recently, however, there has been a global expansion of systematic surveillance and testing for influenza virus among patients admitted to hospital for severe respiratory infection. Here, the researchers use this expanded surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide between 1982 and 2012. Specifically, they undertake a systematic review to identify published research articles on influenza-associated respiratory disease in hospitalized children, and, by aggregating the data from these articles with data collected by hospital-based influenza surveillance, they calculate a pooled estimate of the proportion of children hospitalized with respiratory disease who are positive for influenza. What Did the Researchers Do and Find? Using predefined search criteria, the researchers identified 108 published research articles that provided information on influenza-associated respiratory illness among hospitalized children. In addition, the Global Respiratory Hospitalizations–Influenza Proportion Positive (GRIPP) working group provided 37 hospital-based influenza surveillance datasets. By aggregating the data from these sources using a statistical approach called meta-analysis, the researchers calculated that, overall, influenza was associated with 9.5% of hospitalizations for severe respiratory infection among children under 18 years old worldwide, ranging from 4.8% among children under six months old to 16.4% among children aged 5–17 years. The researchers also calculated that, on average over the study period, influenza resulted in about 374,000 hospitalizations annually among children under one year old (including 228,000 hospitalizations among children less than six months old) and nearly one million hospitalizations annually among children under five years old. Finally, the researchers calculated that influenza-associated hospitalization rates among children under five years old over the study period were more than three times higher in resource-limited countries than in industrialized countries (150 and 48 hospitalizations, respectively, per 100,000 children per year). What Do These Findings Mean? Differences in hospitalization practices, in applications of case definitions, and in influenza testing protocols between settings may affect the accuracy of these findings. Specifically, the approach taken by the researchers may mean that their estimate of the total burden of severe respiratory disease due to influenza is an underestimate of the true situation. Even so, these findings suggest that influenza is an important contributor to hospitalizations for severe respiratory illness among children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could, therefore, reduce the contribution that influenza makes to hospitalizations for respiratory infections among children. Importantly, the estimates of the burden of influenza provided by these findings can now be used by countries considering influenza vaccination programs for children and/or pregnant women to help them investigate the possible health and cost implications of such programs and should also stimulate further research into the development of effective influenza vaccines for young children. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001977. The UK National Health Service Choices website provides information about respiratory infections, seasonal influenza, influenza vaccination, and influenza vaccination in children The World Health Organization provides information on seasonal influenza (in several languages) and on influenza vaccines The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects seasonal influenza, including information about vaccination, and about children, influenza, and vaccination; its website contains a short video about personal experiences of influenza Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination MedlinePlus has links to further information about influenza and about vaccination (in English and Spanish)

Thailand, where influenza viruses circulate year-round, is one of 22 WHO-designated high-burden countries for tuberculosis (TB). Surveillance for hospitalized respiratory illness between 2003 and 2011 revealed 23 (

Background Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. Methods From 2003–2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse-transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera Results Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children

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 suboptimal 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 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

Cryptococcal antigenemia was common among human immunodeficiency virus-infected patients hospitalized with acute respiratory illness in Thailand. Few clinical differences were evident between antigenemic and nonantigenemic HIV-infected patients. Cryptococcal infection was a possible etiologic agent of pulmonary disease in many antigenemic patients., Background. Cryptococcal meningitis (CM) is a major cause of death among HIV-infected patients. Cryptococcal antigenemia (CrAg+) in the absence of CM can represent early-stage cryptococcosis during which antifungal treatment might improve outcomes. However, patients without meningitis are rarely tested for cryptococcal infection. We evaluated Cryptococcus species as a cause of acute respiratory infection in hospitalized patients in Thailand and evaluated clinical characteristics associated with CrAg+. Methods. We tested banked serum samples from 704 human immunodeficiency virus (HIV)–infected and 730 HIV-uninfected patients hospitalized with acute respiratory infection from 2004 through 2009 in 2 rural provinces in Thailand for the presence of CrAg+. Retrospective chart reviews were conducted for CrAg+ patients to distinguish meningeal and nonmeningeal cryptococcosis and to identify clinical characteristics associated with CrAg+ in patients with and without evidence of CM. Results. CrAg+ was found in 92 HIV-infected patients (13.1%); only tuberculosis (19.3%) and rhinovirus (16.5%) were identified more frequently. No HIV-uninfected patients were CrAg+. Of 70 CrAg+ patients with medical charts available, 37 (52.9%) had no evidence of past or existing CM at hospitalization; 30 of those patients (42.9% of all CrAg+) had neither past nor existing CM, nor any alternate etiology of infection identified. Dyspnea was more frequent among CrAg+ patients without CM than among CrAg– patients (P = .0002). Conclusions. Cryptococcus species were the most common pathogens detected in HIV-infected patients hospitalized with acute respiratory infection in Thailand. Few clinical differences were found between antigenemic and nonantigenemic HIV-infected patients. Health care providers in Thailand should evaluate HIV-infected patients hospitalized with acute respiratory infection for cryptococcal antigenemia, even in the absence of meningitis.

Please cite this paper as: Chittaganpitch et al. (2012) Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004–2010. Influenza and Other Respiratory Viruses 6(4), 276–283. Background The re-emergence of avian influenza A (H5N1) in 2004 and the pandemic of influenza A (H1N1) in 2009 highlight the need for routine surveillance systems to monitor influenza viruses, particularly in Southeast Asia where H5N1 is endemic in poultry. In 2004, the Thai National Institute of Health, in collaboration with the US Centers for Disease Control and Prevention, established influenza sentinel surveillance throughout Thailand. Objectives To review routine epidemiologic and virologic surveillance for influenza viruses for public health action. Methods Throat swabs from persons with influenza-like illness and severe acute respiratory illness were collected at 11 sentinel sites during 2004–2010. Influenza viruses were identified using the standard protocol for polymerase chain reaction. Viruses were cultured and identified by immunofluorescence assay; strains were identified by hemagglutination inhibition assay. Data were analyzed to describe frequency, seasonality, and distribution of circulating strains. Results Of the 19 457 throat swabs, 3967 (20%) were positive for influenza viruses: 2663 (67%) were influenza A and able to be subtyped [21% H1N1, 25% H3N2, 21% pandemic (pdm) H1N1] and 1304 (33%) were influenza B. During 2009–2010, the surveillance system detected three waves of pdm H1N1. Influenza annually presents two peaks, a major peak during the rainy season (June–August) and a minor peak in winter (October–February). Conclusions These data suggest that March–April may be the most appropriate months for seasonal influenza vaccination in Thailand. This system provides a robust profile of the epidemiology of influenza viruses in Thailand and has proven useful for public health planning.

Background. Regions of Thailand reported sporadic outbreaks of A/H5N1 highly pathogenic avian influenza (HPAI) among poultry between 2004 and 2008. Kamphaeng Phet Province, in north-central Thailand had over 50 HPAI poultry outbreaks in 2004 alone, and 1 confirmed and 2 likely other human HPAI infections between 2004 and 2006. Methods. In 2008, we enrolled a cohort of 800 rural Thai adults living in 8 sites within Kamphaeng Phet Province in a prospective study of zoonotic influenza transmission. We studied participants’ sera with serologic assays against 16 avian, 2 swine, and 8 human influenza viruses. Results. Among participants (mean age 49.6 years and 58% female) 65% reported lifetime poultry exposure of at least 30 consecutive minutes. Enrollees had elevated antibodies by microneutralization assay against 3 avian viruses: A/Hong Kong/1073/1999(H9N2), A/Thailand/676/2005(H5N1), and A/Thailand/384/2006(H5N1). Bivariate risk factor modeling demonstrated that male gender, lack of an indoor water source, and tobacco use were associated with elevated titers against avian H9N2 virus. Multivariate modeling suggested that increasing age, lack of an indoor water source, and chronic breathing problems were associated with infection with 1 or both HPAI H5N1 strains. Poultry exposure was not associated with positive serologic findings. Conclusions. These data suggest that people in rural central Thailand may have experienced subclinical avian influenza infections as a result of yet unidentified environmental exposures. Lack of an indoor water source may play a role in transmission.

Inbred mice have been widely used for the study of influenza viruses as a mammalian model, while suitable cell lines derived from murine tissue have been limited. Here, we established several immortalized cell clones from respiratory regions of inbred mice (C57BL/6 and BALB/c) by transformation using simian virus 40 large T antigen expression vector. Twenty-five cell clones from C57/BL and BALB/c, designated as MRDC/C and MRDC/B series, respectively, showed different susceptibility to Thai isolates of influenza A virus H5N1. Two murine cell clones, C6 and B7 which were extensively studied expressed both SAα2,3 and SAα2,6 sialic acid receptors. Interestingly, the 6 Thai patient-derived H5N1 isolates examined showed varied virus propagation efficiency in murine cell clones, although there were only slight differences in their propagation in MDCK and A549 cell lines. The results indicate that the murine cell clones are useful for examining the propagation efficiency of H5N1 viruses in vitro.

To examine the effect of the antigenic drift of H1N1 influenza viruses on herd immunity, neutralization antibodies from 744 sera from Thai healthy volunteers in 2008-2009, who had not been vaccinated for at least the last 5 years, were investigated by microneutralization (MN) and hemagglutination inhibition (HI) assays. Significantly higher MN titers were observed for the H1N1 Thai isolate in 2006 than in 2008. The results indicate that the antigenically drifted virus effectively escaped herd immunity. Since the low neutralization activity of herd immunity against drifted viruses is an important factor for viruses to spread efficiently, continuous sero-epidemiological study is required for public health.